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Cell membrane structures and functions:
- Mass balance and homeostasis
- protein-mediated transport
- vesicular transport
- transepithelial transport
- osmosis and tonicity
- resting membrane potential
Law of mass balance:
if the amount of a substance in the body is to remain constant, any input must be offset by an equal loss
- Execretion- Ex. waste materials
- Metabolism- Ex. production of metabolites
- Clearance: the rate at which a material is removed from the blood by either execretion or metabolism.
- The liver, kidneys, lungs, and skin clear substances from the blood.
If a person eats 12 mg of salt in a day and excretes 11 mg of it in the urine, what happened to the remaining 1 mg?
the remaining salt stays in the body
Glucose metabolism effect on mass balance in the body
Glucose metabolism adds CO2 and water to the body, disturbing the mass balance of these two substances. To maintain mass balance both substances must be either excreted or further metabolized.
- ECF: interstitial fluid and plasma
*the whole body is electrically neutral
*chemical and electrical disequilibrium is due to selective membrane permeability
a pressure gradient moves a large quantity of fluid along with its dissolved and suspended materials
Distribution of solutes in body compartments:
- Na+= high in ECF; low in ICF
- K+= low in ECF; high in ICF
- Cl-= high in ECF; low in ICF
- HCO3-= more in ECF, than ICF but not high in either
- Large anions/ proteins= some in the plasma of ECF; high in ICF
Requires direct or indirect use of ATP
Phagocytosis, exocytosis, and endocytosis
ex: Two compartments are separated by a membrane that is permeable to glucose. Each compartment is filled with 1 M glucose. After 6 hours, compartment A contains 1.5 M glucose and compartment B contains 0.5 M glucose
Indirect/ Direct Active Transport:
- DIRECT: which derives energy directly from ATP; Na+K+ATPase
- INDIRECT: which couples the kinetic energy of one molecule moving down its concentration gradient to the movement of another molecule against its concentration gradient.
uses energy stored in concentration gradient
simple and facilitated diffusion, osmosis
Properties of Diffusion:
- open system/ across partitions
- movement down concentration gradient; from high to low
- until state of equilibrium is reached
- lipid solubility: pass through the lipid core of the membrane
- faster with increased tempertaure (more kinetic E)
- faster with smaller molecules
- slower with increase in distance
- slower across thicker membranes
- faster where there is more surface area
- faster where there is increase concentration gradient
If the distance over which a molecule must diffuse triples from 1 to 3, diffusion takes how many times as long?
takes 9 times as long
Where does the energy for diffusion come from?
Three physical methods by which materials enter cells:
- simple diffusion
- protein mediated transport
- vesicular transport
movement of lipophilic molecules directly through phospholipid bilayer
- faster with increased surface area
- faster with increased concentration gradient
- faster with increased membrane permeability
- slow with increased membrane thickness
*small, non-polar molecules
Which is more likely to cross a cell membrane by simple diffusion: a fatty acid molecule or a glucose molecule?
because its lipophilic the fatty acid is more likely to cross by simple diffusion
Functions of membrane proteins:
- Structural proteins - link cell to matrix
- transporters - water channels
- receptors - hormone receptors
- enzymes - intestinal digestive enzymes
Protein Mediated Trasport:
For lipophobic molecules
Passive (facilitated diffusion) or active transport
Channel or Carrier proteins
form water filled channels that link the intracellular and extracellular compartments. Gated channels regulate movement of substances through them by opening and closing; regulated by ligands, the electrical state of the cell, or by physical changes ie. pressure
for small molecules: H2O, Na+, K+, Ca2+, Cl-
*Aquaporins: family of channels for H2O; all cells have!
*selectively based on diameter and charge
- have gates but they are open most of the time
- "leak channels"
- Chemically gated: controlled by messenger molecule or ligand; molecule binds = gate opens
- Voltage gated: controlled by electrical state of the cell; axons; channel that opens when resting membrane potential changes
- Mechanically gated: controlled by physical state of the cell; temp, stretching of cell membrane, etc. *Inner ear- organ of corti- hairs bending
Why doesn’t glucose cross the cell membrane through open channels?
because its too large
Which kinds of particles pass through open channels?
ions and water molecules
If a channel is lined with amino acids that have a net positive charge, which of the following ions is/are likely to move freely through the channel? Na+, Cl-, K+, Ca2+
a channel lined with positive charges attracts anions, which means Cl- is more likely to move freely through the channel.
- never form a continuous connection between the intracelluar and extracellular fluid. They bind to substrates then change conformations.
- used for small organic molecules; glucose
- ions may use channels or carriers
Name two ways channels differ from carriers.
Channel proteins form continuous connections between the two sides of a membrane and transport molecules more quickly.
- a protein that moves more than one molecule at a time
- Symport or Antiport
Molecules are moved in the same direction, the cotransporters are called:
- Symport Carriers
- Ex: glucose, Na+
Molecules are transported in opposite directions, the cotransporters are called:
- Antiport Carriers
- Ex: Na+/K+ pump
A transport protein that moves only one substrate is called:
Sodium Postassium ATPase
most important primary active transporter; pumps Na+ out of the cell and K+ into the cell
protein mediated diffusion; has same properties as simple diffusion.
Specific, competitive, and saturation
Define the following terms and explain how they differ from one another: specificity, competition, saturation. Apply these terms in a short explanation of facilitated diffusion of glucose.
- specificity- GLUT is specific for hexose sugars
- competition- if two hexoses are present (glucose, fructose) they compete for GLUT binding sites
- saturation- when enough sugar is present, transport saturates
If you give a patient saline soltuion (NaCl):
body volumes are going to INCREASE; osmolarity is going to DECREASE.
Primary Active Transport:
ATP DIRECTLY FUELS!
EX: Na+/K+ pump = Na+/K+ATPase (antiport)
Mechanism of the Na+-K+ATPase
3 Na+ from ICF bind to protein -> ATPase is phosphorylated with Pi from ATP; protein changes conformation -> 3 Na+ released into ECF -> 2 K+ bind from ECF; protein changes conformation -> 2 K+ released in ICF
Secondary Active Transport:
Used stored E from concentration gradient
coupling of E of one molecule with movement of another molecule
Mechanism of SGLT transport:
Na+ binds to carrier (in ECF Na+ is high and glucose is low; in ICF Na+ is low and glucose is high) -> Na+ binding creates a site for glucose -> glucose binding changes carrier conformation -> Na+ released into the cytosol and glucose follows
Name two ways active transport by the Na+-K+-ATPase differs from secondary transport by the SGLT.
The ATPase is an antiporter, but the SGLT is a symporter. The ATPase requires energy from ATP to change conformation, whereas SGLT uses energy stored in the Na+ concentration gradient
What does Na+ movement from the cytoplasm to the extracellular fluid require energy?
Sodium movement out of the cell requires energy because the direction of ion flow is against the concentration gradient.
Movement of large molecules across the cell membrane
- 1. Phagocytosis
- 2. Endocytosis
- 3. Exocytosis
- Requires E
- cell engulfs particle into vesicle via pseudopodia formation
- vesicles formed are much larger than those formed by endocytosis
- phagolysosome = phagosome fused with a lysosome
- Requires E
- membrane surfaces indent
- smaller vesicles
- nonselective: Pinocytosis for fluids and dissolved substances
- when vesicles that come into the cytoplasm are returned to the cell membrane = membrane recycling
Name the two membrane protein families associated with endocytosis.
- clathrin - receptor mediated endocytosis Ex. LDL cholesterol and Familial Hypercholesterolemia; ligands bind to membrane receptors that concentrate in coated pits (site of endocytosis)
- caveolin - potocytosis; receptors are located in caveolae that have a caveolin protein coating
- Intracellular vesicle fuses with membrane; releases its contents into extracellular space
- Requires E and Ca2+
- Active transport
- docking and fusion of vesicles
- Ex: goblet cells, fibroblasts; receptor insertion, waste removal
How do cells move large proteins into the cell? Out of the cell?
proteins move into cells by endocytosis and out of the cell by exocytosis
How does phagocytosis differ from endocytosis?
In phagocytosis, the cytoskeleton pushes the membrane out to engulf a particle in a large vesicle. In endocytosis, the membrane surface indents and the vesicle is much smaller.
- combination of secondary active and passive transport
- molecules must cross two phospholipid bilayers
- Polarity of epithelial cells: apical and basolateral; allows one way movement of molecules across the epithelium
- Na+-glucose transporter
- Na+ leak channels but no water pore
- Na+-K+ATPase and K+ leak channels. May also have water channels
Transepithelial transport of glucose:
Na+ glucose symporter brings glucose into the cell against the concentration gradient using E stored in the Na+ concentration gradient -> GLUT transporter transfers glucose to ECF by facilitated diffusion -> Na+/K+ATPase pumps Na+ out of the cell, keeping ICF Na+ concentration low
- endocytosis -> vesicular transport -> exocytosis
- moves large proteins intact
- Ex: absorbtion of maternal antibodies from breast milk, movement of proteins across capillary endothelium
- the movement of water across a membrane in response to a concentration gradient
- causes volume change
- can be opposed by other force (pressure) so that water does not move
concentration; the number of particles per liter of solution; mOsM
Molarity -> Osmolarity
- 1 M glucose = 1 OsM glucose
- 1 M NaCl= 2 OsM NaCl
- 1 M MgCl2= 3 OsM MgCl2
osmolarity of the human body = 300 mOsM
isosomotic, hyperosmotic, hyposmotic
A tissue placed in a 0.1 OsM NaCl soultion gained H20; therefore...
the soultion was hyposmotic to the tissue
What does it mean if we say that a solution is hypotonic to a cell? Hypertonic to the same cell? What determines the tonicity of a solution relative to a cell?
- hypotonic- net influx of water into the cell
- hypertonic- net water loss
- Tonicity- determined by relative concentrations of nonpenetrating solutes in cell versus solution
Red blood cells are suspended in a solution of NaCl. The cells have an osmolarity of 300 mOsM, and the solution has an osmolarity of 250 mOsM. (a) the solution is: (hypertonic, isotonic, or hypotonic) to the cells? (b) Water would move: (into the cells, out of the cells, or not at all)?
2 M NaCl solution is placed in compartment A and 2 M glucose solution is placed in compartment B. The compartments are separated by a membrane that is permeable to water but not to NaCl or glucose
- The salt solution is HYPEROSMOTIC to the glucose solution;
- True. Water will move from one compartment to another. it will move from compartment B to compartment A.
- physiological term describing volume change of a cell if placed in a solution
- isotonic, hypertonic, hypotonic
- depends on osmolarity & penetrating/ nonpenetrating solutes
cell does not change size
- molecule that is not able to enter cells
- realtive concentrations in the cell and in the solution determine tonicity
- cant enter/ leave cell (sucrose, NaCl)
- water will move to dilute
- molecule that moves freely between the intracellular and extracellular compartments
- contribute to the osmolarity of a solution but not to its tonicity
- can enter cell (glucose, urea)
- distribute to equilibrium
Resting membrane potential
IC and EC compartments are in electrical disequilibrium
- K+ = intracellular cation
- Na+ = extracellular cation
Water = conductor/ cell membrane = insulator enables separation of charges (and molecules) in body
- K+ moves down concentration gradient from inside to outside of the cell
- Excess - charges in cell
- electrical gradient created pulls k+ back into cell
Na+/K+ATPase pumps out 3Na+ for 2K+ pumped into the cell
allowed for by cell membrane; inside of cells negative relative to the extracellular fluid
Created by: diffusion, active transport, selective membrane permeability to certain ions and molecules
membrane potential= unequal distribution of charges across cell membrane
Explain the differences between a chemical gradient, an electrical gradient, and an electrochemical gradient.
chemical gradient = concentration gradient. Electrical gradient = separation of electrical charge. Electrochemical gradient includes both concentration and electrical gradients.
Resting membrane potential difference:
- the electrical gradient between the extracellular fluid and intracellular fluid
- all cells have it
Equilibrium potential for K+ and Na+
- the membrane potential that exactly opposes the concentration gradient of an ion
- K+ = -90 mV
- Na+= 60 mV
Beta cells at rest:
decrease glucose in blood -> slows metabolism -> ATP decreases -> KATP channels open -> Ca2+ channel closed; cell at resting membrane potential; no insulin released
Beta cells secrete insulin:
increase glucose in blood -> metabolism increases -> ATP increases -> KATP channels close -> cell depolarizes; a Ca2+ channels open -> Ca2+ entry acts as intracellular signal -> Ca2+ signal triggers exocytosis and insulin is secreted
- CFTRs are chemically gated channel proteins
- CFTR proteins are on the apical surface
- If Cl- cannot be secreted into the airways, there will be no fluid movement to thin the mucosa
- Taking artificial enzymes will help enable the digestion of food.
Cell to Cell communication:
signals: nervous (electrical) and chemical
- direct cytoplasmic transfer
- contact dependent signals
- short distance (local)
- long distance (combination of signals)
Target cell receives signal
- Gap Junctions: protein channels that connect two adjacent cells. when they are open, chemical and electrical signals pass directly from one cell to the next
- everywhere; but particularly in heart and GI tract muscle
- Paracrines and Autocrines: chemical signals secreted by cells
- transport by diffusion
- Ex. histamines, cytokines, eicosanoids
- chemicals that act on cells in the immediate vincinity of the cell that secreted the paracrine;
- by diffusion
chemical signal that acts on the cell that secreted it
Long Distance Communication:
- Endocrine system communicates by hormones secreted in the endocrine glands, transported to the bloodstream to the target cells by diffusion
- the only cells that have receptors for hormones are target cells
- Nervous system uses electrical and chemical signals; neurocrine molecules
- regulatory peptides that control cell development, differentiation, and the immune response. Both local and long distance signals.
- every nucleated cell can make them
- broader target range
- made upon demand - no storage
- involved in cell development and immune response
- may exhibit autocrine action, signaling cells that produce them
Signal molecule (cytokine, autocrine, hormone, paracrine) -> Receptor (protein/ lipid; on target cell; some are inside) *dont have to have a receptor for lipid hormone -> Intracellular signal -> target protein -> Response
pathways use membrane receptor proteins and intracellular second messenger molecules to translate signal information into an intracellular response
signal molecule -> binds to membrane receptor -> activates protein ->:
amplifer enzymes-> second messenger-> increase Ca2+ -> calcium binding proteins -> cell response
protein kinases-> phosphorylated protein -> cell response
- Cytosolic or Nuclear: enters cells (slower); lipophilic
- Cell membrane: cannot enter cell (faster); lipophobic
signal molecule binds to G-protein linked receptor; activates G-protein -> G-protein turns on adenylyl cyclase (amplifer enzyme) -> converts ATP to cyclic AMP -> cAMP activates protein kinase A -> protein kinase A phosphorylates other proteins; leading ultimately to a cellular response
Membrane Receptor classes:
- chemically gated channels: Ach receptor; sodium channel *most rapid signal pathway
- singal transduction: Receptor enzymes: activate protein kinase (tyrosine kinase), or amplifier protein (guanylyl cyclase), which produces second messenger cGMP.
- G-protein-coupled: open ion channels or alter intracellular enzyme activity *most common for protein and peptide hormones
What happens during amplification?
Amplification turns one signal molecule (first messenger) into multiple second messenger molecules.
Novel Signal Molecules: Ca2+
- Ca2+ is an important signal molecule that binds to calmodulin to alter enzyme activity; also binds to other cell proteins to alter movement and initiate exocytosis.
- can enter cell via voltage, ligand, and mechanically gated channels
- intracellular storage: sarcoplasmic reticulum
- leads to movement of contractile proteins (myosin) and exocytosis of vesicles
Novel Signal Molecules: NO and CO
- Nitrous Oxide: activates guanylyl directly
- made from arginine
- short acting auto- and paracrine
- in brain and blood vessels
Carbon Monoxide: in nervous tissue and smooth muscle; short lived signal gases
Novel Signal Molecules: Eicosanoids
arachidonic acid derivative: creates lipid signal molecules: Leukotrienes (asthma), prostanoids (everywhere) important for inflammation
*signal receptor molecules exhibit: specificity, competition, and saturation
Modulation of Signal Pathways:
- response of cell to a signal molecule is determined by the cells receptor for the signal
- agonist: mimic the action of a signal molecule
- antagonist: block signal pathway
What is the difference between a first messenger and a second messenger?
first messengers are extracellular; second messengers are intracellular
If a cell is going to move calcium ions from its cytosol to the extracellular fluid, will it use passive or active transport?
The cell must use active transport to move Ca2+ against its concentration gradient
What are two routes for long distance signal delivery in the body?
neurons and blood
adds the functional group phosphate to its substrate by transferring it from an ATP molecule
intracellular effector in chemical signaling
Physiological response loop
stimulus, receptor, afferent pathway, integrating center, efferent pathway, effector, response
allows the parameter to be increased or decreased by a single signal
one hormone or neuron increases the parameter while another decreases it
Why do steroid hormones not require signal transduction and second messengers to exert their action?
Steroids are lipophilic, so they can enter cells and bind to intracellular receptors
To decrease a receptors binding affinity, a cell might:
- synthesize a new isoform of the receptor
- use a covalent modulator
What is the difference between tonic control and antagonistic control?
tonic control usually involves one control system but antagonistic control uses two
What is the difference between local control and reflex control?
local control takes place in or very close to the target cell. Reflex control is mediated by a distant integrating center
seven steps in a reflex control pathway:
stimulus, sensor or sensory receptor, afferent pathway, integrating center, efferent pathway, target or effector, response
the minimum stimulus to trigger a response
desired target value for a parameter
the organ or gland that performs the change
movement of a parameter within the desired range
daily fluctuations of body functions, including blood pressure, temperature, and metabolic processes is:
List two ways a cell may decrease its response to a signal:
it may down-regulate receptor number or decrease receptor affinity for the substrate
- Efferent: output signal from integrating center to target (nerve or hormone)
- Afferent: input pathway from stimulus to integrating center (sensory nerve)
- Effector: target cell or tissue that carries out the response (muscle)
- Stimulus: change that begins a response (touching a hot stove)
- Receptor (sensor): cell that perceives the stimulus (temp receptor)
- Integrating center: cell or cells that receive information, decides action, send signal (to brain) to initiate response
- Response: what target cell does to react to stimulus (pull hand away from hot stove)
Explain the differences among positive feedback, negative feedback, and feedforward mechanisms
- Negative feedback: feedback signal turns response loop off; helps maintain homeostasis.
- Positive feedback: feedback keeps the response loop going; makes change bigger
- Feedforward: starts response loop before the stimulus does; minimizing change
neural versus endocrine control mechanisms
Neural control is faster than endocrine and better for short-acting responses. Endocrine can affect widely separated tissues with a single signal and better for long-acting responses.
Label, positive or negative feedback:
- glucagon secretion in response to declining blood glucose NEGATIVE
- increasing milk letdown and secretion in response to more suckling POSITIVE
- urgency in emptying ones urinary bladder NEGATIVE
- sweating in response to rising body temperature NEGATIVE
- The problem in type 2 diabetes could be a defective signal transduction mechanism
- In type 1 diabetes insulin levels are low so type 1 is more likely to cause up-regulation of the insulin receptors
- insulin decreases blood glucose levels, glucagon increases them; they are antagonists
- glucose is lipophobic; must cross membrane by facilitated diffusion; if a cell lacks protein carriers, facilitated diffusion cannot take place
- when blood glucose levels fall a negative feedback loop is operating
- a chemical secreted by a cell or group of cells into the blood for transport to a distant target, where its effective a very low concentrations.
- specificity depends on its receptors and their associated signal transduction pathways
- bind to receptors; on the surface or inside the cell
- action of limited duration (half-life)
- the study of hormones: Endocrinology
Classifications of hormones:
- Peptide and protein; most common
- Steroid; made from cholesterol; lipophilic
Peptide (protein) hormones:
- composed of three or more amino acids
- preprohormones -> prohormones -> hormones
- dissolve in plasma and have a short half-life
- bind to surface receptors on their target cells to initiate rapid cellular response through signal transduction
- peptide hormones also initiate synthesis of new proteins
- cAMP 2nd messenger system is most commom
- synthesized on smooth ER
- no storage; synthesized as needed; released through lipophilic membrane
- transport by attaching to proteins because they are hydrophobic and dont like blood
- longer half-life
- binds to receptor inside the cell; turns genes on and off and direct synthesis of new proteins
- stimulates transcription/ translation inside nucleus
- steriod hormones not bound to carriers can diffuse
- only cells with receptors will respond
- bound with membrane receptors will have nongenomic effects
- type of reaction depends on kind of receptor
- synthesized as needed
- amino acid derived
- smaller hormones
- behave like steriod and peptide hormones
- have -COOH and NH2
- Ex. Melatonin, adrenaline (catecholamines- behave like peptide hormones), thyroid hormone (behave like steroid hormones)
- like peptide hormones - bind to surface receptors
- Ex. dopamine, norepinephrine, epinephrine (adrenaline)
- have Iodine
- without iodine you cannot make thryroid hormone
- iodine is from salt/ seafood
Steroid Hormon Action:
steriod hormone receptors are in cytoplasm or nucleus -> some bind to membrane receptors; use 2nd messenger system to create rapid response -> receptor-hormone binds to DNA; activates or represses genes -> activated genes create new mRNA goes into cytoplasm -> traslation produces new protein
Control of Hormone Release:
- pure endocrine pathway lacks afferent pathway
- integration in endocrine cell
- output signal: hormone/ neurohormone Efferent pathway
- negative feedback turns off reflex
- endocrine cells act as both sensor and integrating center in a simple reflex pathway
Simple Endocrine Reflex:
endocrine cells act as sensor AND integrating center -> no afferent pathway -> responds by secreting hormone
Ex. Parathyroid Hormone (PTH) -> Ca2+ in plasma increase; Effector organs: bones, intestines, kidneys
antagonist: calcitonin from thyroid
- stimulus= low plasma Ca2+
- sensor/ integrating cell= parathyroid cell
- efferent pathway= parathyroid hormone
- effector= bone and kidney
- tissue response= bone absorbtion, kidney absorbtion, intestine absorbtion
- systemic response= increased plasma Ca2+
- NH released by modified neurons upon NS signal
- Catecholamines: from adrenal medulla
- Hypothalamic NH from posterior pituitary ex. oxytocin, ADH/ Vasopressin
- Hypothalamic NH from anterior pituitary via hypophyseal portal system
2 capillary beds in series
- in our:
- hypophyseal portal vein
- hepatic portal vein
NH of Posterior Pituitary:
- oxytocin and ADH/ Vasopressin
- active transport
- anterograde axonal transport
- both peptides transported in secretory vesicles via axonal transport
NH of Anterior Pituitary:
prolactin -> breast, TSH -> thyroid gland -> thyroid hormone -> many tissues, ACTH-> adrenal cortex -> cortisol -> many tissues, GH -> liver -> IGFs -> many tissues, FSH& LH -> endocrine glands of gonads -> androgens, estrogen, progesterone -> many tissues & germ cells of gonads
trophic hormone: controls secretion of another hormone
Complex Endocrine Reflex:
- hormones act as negative feedback signals
- short loop vs long loop
- the hypothalamic trophic hormones reach the pituitary through hypothalamic-hypophyseal portal system
multiple hormones can affect a single target simultaneously
- the interaction if the combination of two or more hormones yeilds a result that is greater than additive
- glucagon + epinephrine + cortisol
- If one hormone cannot exert its effects fully unless a second hormone is present; the second is permissive to the first
- Hormone A will not exert full effect without presence of hormone B
- Ex. thyroid and growth hormone
- works better with the other
- opposing action
- one hormone opposes the action of another
- Ex. Insulin and glucagon
- compete for the same receptor
- activate different opposing metabolic pathways
unbalance leads to diesease
- Hypersecretion: too much
- Hyposecretion: not enough ex. type 1 diabetes
- Abnormal target tissue response: not responding ex. type 2 diabetes
- latrogenic (gland shrinks)
- Dr. induces
Ex. Cushing's syndrome, gigantism, Graves disease (Hyperthyroidism)
- atrophy of gland (destroyed)
- gland shrinks
- gland doesnt produce hormone
Ex. addison's disease, dwarfism, hypothyroidism
Pituitary makes more TSH because cant make T3/T4 results in goiter (enlarged thyroid)
- Causes: ABS attack thyroid gland
- surgical removal of thyroid gland
- radioactive iodine treatment
- external radiation
- iodine deficiency
- arise in the last endocrine gland in a reflex
- ex. thyroid gland, adrenal cortex, testes/ ovaries
- a problem with one of the tissues producing trophic hormones
- ex. hypothalamus, pituitary
Cortisol Hypersecretion Scenario:
- decreased CRH -> decreased ACTH -> increased cortisol
- primary endocrine disorder
*increased CRH or ACTH would be secondary
- antibodies from lymphocytes (TSI) bind to TSH receptor and stimulate thyroid hormone production
- immunoglobulin = antibody
- this activation by TSI is not subject to the normal negative feedback loop
- increases metabolism of cells
Normal: 4.6-12 ug/dl of T4 and 0.5-6 uU/ ml of TSH
Graves Disease: 14 ug/dl of T4 and 0.25 uU/ml of TSH
Name the membrane transport process by which glucose moves from the extracellular fluid into cells
glucose enters the cells by facilitated diffusion (GLUT transporters)
Based on what you know about organelles involved in protein and steroid synthesis, what would be the major differences between the organelle composition of a steroid-producing cell and that of a protein-producing cell?
a steroid producing cell would have extensive smooth endoplasmic reticulum; a protein producing cell would have lots of rough endoplasmic reticulum and secretory vesicles.
In the blood glucose example, the increase in blood glucose corresponds to which step of a reflex pathway? Insulin secretion and the decrease in blood glucose correspond to which steps?
Increased blood glucose is the stimulus. insulin secretion is the efferent pathway; decrease in blood glucose is the response.
what is the target tissue of a hypothalamic hormone secreted into the hypothalamic-hypophyseal portal system?
the target is endocrine cells of the anterior pituitary
What event serves as a negative feedback signal to shut off insulin release?
The pathway shuts off when food is no longer present in the intestine to create stretch. A decrease in blood glucose can also serve as a negative feedback signal.
List the three basic ways hormones act on target cells:
- alter rate of enzymatic reactions
- control transport of molecules into and out of cells
- change gene expression and protein synthesis in target cells
Decide if each of the following characteristics applies best to peptide hormones, steroid hormones, both classes, or neither.
- are lipophobic and must use a signal transduction system PEPTIDE
- have a short half-life, measured in minutes PEPTIDE
- often have a lag time of 90 mins before effects are noticable STEROID
- are water soluble, and thus easily dissolve in the extracellular fluid for transport PEPTIDE
- most hormones belong to this class PEPTIDE
- are all derived from cholesterol STEROID
- consist of three or more amino acids linked together PEPTIDE
- are released into the blood to travel to a distant target organ ALL
- are transported in the blood bound to protein carrier molecules STEROID
- are all lipophillic, so diffuse easily across membranes STEROID
Why do steroid hormones usually take so much longer to act than peptide hormones?
Steroid hormones usually initiate new protein synthesis, which takes time; peptides modify existing proteins.
What characteristic defines neurohormones?
hormones synthesized by and secreted by neurons
What is hypothalamic-hypophyseal portal system? Why is it important?
The portal system is composed of hypothalamic capillaries that take up hormones and deliver them directly to capillaries in the anterior pituitary. The direct connection allows very small amounts of hypothalamic hormone to control the anterior pituitary endocrine cells.
Organization of the NS:
CNS: brain -> cranial nerves and spinal cord -> spinal nerves --> Afferent (sensory) -> Efferent (motor) -> somatic -> ANS --> Sympathetic, Parasympathetic
Cells of the NS:
- nerve cell = neuron; excitable, can generate and carry electrical signals
- mutipolar: somatic motor
- unipolar: sensory
- bipolar: rare
- support cells = neuroglia
- materials transported between cell body and axon terminal
- slow: carries enzymes that are not quickly consumed
- fast: utilizes kinesins (move vesicles down), dyneins (move vesicles up) and microtubules
- Schwann (form myelin sheath) and satellite cells are in PNS
- Microglia (modified immune cells that act as scavengers), oligodendrocytes, astrocytes, ependymal cells are in the CNS
Neural Stem Cells:
develop into new neurons and glia are found in the ependymal layer as well as in other parts of nervous system
Nodes of Ranvier:
seconds of uninsulated membrane occuring at intervals along the length of an axon
Membrane Potential is influenced by:
- concentration gradients of ions across the membrane
- the permability of the membrane to those ions
predicts membrane protential based on ion concentration gradients and permeability
means inside becomes more positive
Na+ and Ca2+
inside becomes more negative
Gated ion channels control membrane permeability:
- mechanically: pressure, stretch, touch
- chemically: ligand
- voltage: change in membrane potential
Voltage-gated Na+ channel function:
- Resting membrane potential activation gate closes channel
- Depolarization stimulus arrives at channel -> gate opens
- With activation gate open, Na+ enters cell
- Inactivation gate closes; Na+ entry stops
- During repolarization caused by K+ leaving cell, gates reset
- resting membrane potentials
- variable strength
- travel over short distances only
- depolarizations or hyperpolarizations whose strength is directly proportional to the strength of the triggering event. Graded potentials lose strength as they move through the cell.
- constant strength
- travel rapidly over longer distances - never loses strength
- rapid electrical signals that travel undiminished in amplitude from the cell body to the axon terminals
- start at axon hilcock- because we have v-gated sodium channels that open in response to depolarization of cell
Signal movement through neuron:
- input signal (graded potential)
- integration of input signal at trigger zone
- conduction signal to distal part of neuron (action potential)
- output signal (neurotransmitter)
ion movement across membrane
increase in Na+ permeability -> Na+ enters cel down electrochemical gradient -> influx causes depolarization of membrane potential = electrical signal
absolute refractory period:
a second action potential cannot be triggered, no matter how large the stimulus. action potentials cannot be summed
relative refractory period:
higher than normal graded potential is required to trigger an action potential
apparent jumping of action potential from node to node
electricl signal passes directly from cytoplasm of one cell to another through gap junction
use neurotransmitters to carry information from one cell to the next
acetylcholine, norepinephrine , glutamate, GABA, serotonin, adenosine, and nitric oxide
- ligand-gated ion channels
- G protein-coupled receptors
Where do neurons that secrete neurohormones terminate?
neurons that secrete neurohormones terminate close to blood vessels so that the neurohormones can enter the circulation
What is the primary function of each of the following: myelin, microglia, ependymal cells?
Myelin insulates axon membranes. Microglia are scavenger cells in the CNS. Ependymal cells form epithelial barriers between fluid compartments of the CNS.
Would a cell with a resting potential of -70 mV depolarize or hyperpolarize in the following cases?
- cell becomes more permeable to Ca2+ DEPOLARIZE
- cell becomes less permeable to K+ DEPOLARIZE
would the cell membrane depolarize or hyperpolarize if a small amount of Na+ leaked into the cell?
When Na+ channel gates are resetting, is the activation gate opening or closing? Is the inactivation gate opening or closing?
During resetting, the activation gate is closing and the inactivation gate is opening
Which organelles are needed to synthesize proteins and package them into vesicles?
proteins are synthesized on the ribosomes of the rough endoplasmic reticulum; then the proteins are directed into the golgi complex to be packaged into vesicles
How do mitochondria get to the axon terminals?
Mitochondria reach the axon terminal by fast axonal transport along microtubules
One class of antidepressant drugs is called selective serotonin reuptake inhibitors SSRIs. What do these drugs do to serotonin activity at the synapse?
SSRIs decrease reuptake of serotonin into the axon terminal, thereby increasing the time serotonin is active in the synapse.
why are axon terminals sometimes called “biological transducers”?
axon terminals convert (transduce) the electrical action potential signal into a chemical neurotransmitter signal
List three functional classes of neurons, and explain how they differ structurally and functionally.
Afferents carry messages from sensory receptors to CNS. Cell bodies are located close to the CNS. Interneurons are completely contained within the CNS and are often extensively branched. Efferent carry signals from the CNS to effectors. They have short, branched dendrites and long axons.
process of a neuron that receives incoming signals
sensory neurons, transmit information to CNS
neuron that transmits information from CNS to the rest of the body
region of neuron where action potential begins
long process that transmits signals to the target cells
Axonal transport refers to the:
movement of organelles and cytoplasm up and down the axon. not all use microtubules and not all substances moved will be secreted.
List the four major types of ion channels found in neurons. Are they chemically gated, mechanically gated, or voltage gated?
- Na+ channels: voltage-gated along axon; ligand-gated or mechanically gated on dendrites
- K+ channels: voltage gated along axon
- Ca2+ channels: voltage gated in axon terminal
- Cl- channels: chemically gated
What is the myelin sheath?
insulating membranes around neurons that prevents current leak
List two factors that enhance conduction speed.
diameter of the axon and presence or absence of myelin
List two ways neurotransmitters are removed from the synapse
enzymatic degradation, reabsorption and diffusion
What causes depolarization phase of an action potential?
Na+ entering the cell through voltage-gated channels
sequence of events after a neurotransmitter binds to a receptor on a postsynaptic neuron:
- ligand-gated ion channel opens
- cell depolarizes
- local current flow occurs
- graded potential occurs
- trigger zone reaches threshold
- voltage-gated Na+ channel opens
- cell depolarizes
- action potential fires at axon hillock
- saltatory conduction occurs
- voltage-gated Ca2+ channel opens
The cell in question has a resting membrane potential of -70 mV; hyperpolarize, depolarize, or repolarize?
- membrane potential changes from -70 mV to -50 mV DEPOLARIZE
- membrane potential changes from -70 mV to -90 mV HYPERPOLARIZE
- membrane potential changes from +20 mV to -60 mV REPOLARIZE
- membrane potential changes from -80 mV to -70 mV DEPOLARIZE
A neuron has a resting membrane potential of -70 mV. Will the neuron hyperpolarize or depolarize when each of the following occur:
- Na+ enters the cell DEPOLARIZE
- K+ leaves the cell HYPERPOLARIZE
- Cl- enters the cell HYPERPOLARIZE
- Ca2+ enters the cell DEPOLARIZE
An unmyelinated axon has much greater requirement for ATP than a myelinated axon of the same diameter in length. Explain why
unmyelinated axons have many ion channels, so more ions cross during an action potentials and must be returned to their original compartments by the Na+-K+-ATPase, using energy from ATP.
Information Transfer at the synapse:
Action potenil depolarizs the axon terminal
Depolarization opens voltage-gated Ca2+ channels and Ca2+ enters cell
Calcium entry triggers exocytosis of synaptic vesicle contents.
Neurotransmitter diffuses across the synaptic cleft and binds with eceptors on the postsynaptic cell.
neurotransmitter binding initiates a respons in the postsynaptic cell.