Physio Muscle Physio (9)

• contracts (shortens) quickly & its duration of contraction tends to be short-lived
• neuromuscular transmission is required for contraction (it will never contract if neurons are inactive)
• there is NO communication between individual skeletal muscle fibers

• contracts quickly & does so for a long time → a single action potential results in continuous contraction
• contracts spontaneously: neuronal innervation isn't needed for a contraction to occur, it just modulates it
• gap junctions between myocytes allow for intercellular communication between the entire myocardium

• neuromuscular transmission (APs) can initiate contraction in some types but only modulates contraction in other types (may or may not need stimulation from a neuron in order to contract)
• its contractions are weak compared to those of skeletal/cardiac muscle & the muscle contracts very slowly
• gap junctions support intercellular communication between some types of smooth muscle myocytes but not others

• RED (slow twitch): many mitochondria & oxidative enzymes (AERobic); don't contract fast but CAN contract for long periods without fatiguing, eg. back muscles
• WHITE (fast twitch): bigger muscle cells, contract quickly; fewer mitochondria & oxidative enzymes (ANaerobic); quicker to fatigue, eg. quadraceps

• are small in diameter, are innervated by smaller diameter motor axons → are less strong but have sustained contractions
• have fewer glycolytic enzymes
• a less extensive sarcoplasmic reticulum results in a SLOW release of Ca²⁺
• contain MANY mitochondria
• have a dense capillary network that contributes to a high O₂ supply
• contain lots of myoglobin, an O₂ binding
• protein that causes muscle to be Red

• are large in diameter, are innervated by larger diameter motor axons → have a lot of strength but fatigue quickly
• have a lot of glycolytic enzymes
• an extensive sarcoplasmic reticulum results in RAPID release of Ca²⁺
• contain FEW mitochondria
• have a limited blood supply & a low oxidative metabolism

• white (Fast) are very good at producing STRONG contractions but b/c they don't derive their energy from aerobic metabolism (are anaerobic, contain few mitochondria) they FATIGUE more easily
• a forceful quick contraction = fast (white) twitch
• a sustained contraction = slow (red) twitch
• most muscles have a MIXTURE of red & white fiber types in them

• each cell is innervated by 1 or more autonomic motor neurons
• action potentials are usually absent & contraction is triggered by neurotransmitters (NE or ACh)
• there is little to no electrical coupling between cells (can have tension in different parts of the organ)

FINER motor control results from no electrical coupling

• each myocyte doesn't have individual motor nerve innervation - there are gap junctions & extensive electrical coupling between cells so a contraction in one can spread to others (like cardiac muscle)
• myocytes usually spontaneously activate
• contraction is only modulated by neurotransmitters (NE or ACh)
• (unitary smooth muscle can contract without nerve stimulation)

• whole muscle
• ↓
• Fasiculus
• ↓
• Muscle Fiber (myocyte) = muscle cell
• ↓
• Myofibril: very long chains of sarcomeres
• ↓
• Sarcomeres: contractile units of the cell; made of thin & thick filaments
• ↓
• Myofilaments: actin & myosin
• 

• I band: light staining thin actin filament bisected by the Z line
• Z line: serves as an anchoring point for thin actin filaments (Z disk)
• Sarcomere exists from the dark Z line in one thin actin filament to the Z line in the next
• A band: dark staining THICK myosin filaments
• M line: line w/ proteins that reside in the middle of the A (thick myosin) band: hold the myosin together
• H band: slightly lighter area surrounding M line in the middle of the A (dark, myosin) band
• the bubbly/dotty stuff between myofibril striation = cell organelles (eg. mitochondria)

• muscle contraction is produced by actin & myosin filaments sliding past each other
• the Sarcomere overall shortens → a 'domino' effect of sorts that can cause the muscle to shorten by ~10% overall
• the Z-lines move CLOSER together
• neither the I nor A bands shorten (Z within the I band just moves)
• H band (surrounding M line) disappears - is filled in with thin filaments
• 

• when the muscle is too shortened/contracted OR overstretched only a low force can be generated (aka overly short or overly long sarcomere length)
• the best position for optimal force generation is when the sarcomere is at some intermediate length; this corresponds to where maximal TENSION can be generated
• 

• in skeletal muscle this consists of actin, tropomyosin, & troponin
• the filament itself is a double stranded helical polymer of actin molecules
• contains no cross-bridges
• has myosin-binding sites where myosin heads may bind
• F-actin is associated with 2 regulatory proteins: tropomyosin & troponin

• 2 identical helices that coil around each other & sit in the groove between the 2 wound actin filaments
• active state: makes myosin-binding sites on actin accessible to myosin heads
• resting state: covers the binding sites; it interferes with the binding of myosin to actin when the muscle is relaxed
• 

• controls tropomyosin by pulling it away from the myosin-binding site on actin filaments in the presence of Ca²⁺
• troponin T which binds to a single molecule of tropomysoin
• troponin C binds Ca²⁺
• troponin I binds to actin & inhibits contraction when bound ("I" for actin = I band & "Inhibits")

it allows for the binding of actin to myosin to be regulated by local changes in intracellular Ca²⁺

• an in increase in intracellular Ca²⁺ of course
• in all 3 types of muscle Ca²⁺ acts through regulatory proteins, not by direct interaction with the contractile proteins themselves

• bipolar assemblies of multiple myosin-II molecules, a double trimer made up of 2 intertwined heavy chains, two regulatory light chains, & two other “alkali” or “essential” light chains
• the heads of the heavy chains each can both bind to actin & have an enzymatic site for binding & hydrolyzing ATP
• the “alkali” light chain plays an role in stabilizing the head region
• the regulatory light chain regulates myosin ATPase activity & is itself regulated by Ca²⁺-dependent & Ca²⁺-independent kinases
• 

• responsible for generating the sliding movement of myosin along actin filaments that produces muscle contraction
• 0. Rest. ATP is bound to the myosin head & hydrolyzed but the energy of the reaction can't be released...
• 1. …UNITL the myosin head binds to actin
• 2. the release of the hydrolysis products is associated with the power stroke
• 3. the rotated & still-attached cross bridge is now in the rigor state
• 4. detachment occurs when a new ATP molecule binds to the myosin head
• 5. the ATP is hydrolyzed, activating the myosin head so it can rotate when [Ca²⁺] increases & bind to actin again
• 

• the cyclic reactions will continue as long as there is an ATP supply & the Ca²⁺ concentration (what's activating it) is maintained
• ATP binding to the myosin head allows the head to dissociate from actin & rotate back to the resting state
• the energy of ATP hydrolysis is stored in the unbound “resting” myosin head
• Ca²⁺ promotes binding of the myosin head to actin; this releases the stored energy causing the cross bridge to rotate, forcing the filaments to slide over one another

• Ca²⁺ binds to calmodulin (a protein similar to troponin C), causing it to activate myosin light chain kinase (MLCK)
• the activated MLCK phosphorylates the regulatory light chain of myosin, increasing its ATPase activity, allowing myosin to bind to actin & initiate contraction
• the energy for crossbridge cycling is NOT stored in the myosin head, but must be generated by ATP hydrolysis before contraction can begin

the processes by which excitation (electrical activity at the cell surface) leads to an increase in the concentration of intracellular Ca²⁺

• muscle fibers are larger in diameter than the post-synaptic structure in synapses, therefore having voltage dependent Ca²⁺ channels only on the surface of a myocyte membrane ISN'T going to do much
• T (transverse) tubules solve this problem: are indentations of plasma membrane ~ every 2 sarcomeres that invaginate DEEP into the muscle fiber
• have voltage dependent gates expressed on T tubule surface → gets Ca²⁺ signal into the depths of the muscle

• through the release of Ca²⁺ from the sarcoplasmic reticulum - cisterns of smooth ER (membrane bound compartments) full of Ca²⁺ surrounding T tubules
• voltage dependent Ca²⁺ channels in T tubules trigger the release of Ca²⁺ from big stores in the sarcoplasmic reticulum

• 1. action potentials are propagated from the NMJ along the skeletal muscle membrane & down T-tubules
• 2. when the triad region of the T-tubules is depolarized, L-type Ca²⁺ channels (clustered in groups of four in the T-tubule membrane) are activated

• L-type voltage-gated Ca²⁺ channels found on the T-tubule membrane
• function as the voltage sensor in EC coupling
• each of the four voltage-gated Ca²⁺ channels are called DHP receptor b/c they're inhibited by dihydropyridines

• 1. Ca²⁺ enters the cytosol through the 4 channel pores
• 2. a conformational change occurs in Ca²⁺-release channels located in the SR membrane→ SR Ca²⁺ release

• voltage-gated Ca²⁺ channels found on the sarcoplasmic reticulum membrane
• *the interaction between the T-tuble L-type Ca²⁺ channels & the closely associated SR Ca²⁺-release channels is the BASES for SR Ca²⁺ release
• are inhibited by a class of alkaloids including ryanodine, a plant alkaloid

• passage of small amounts of Ca²⁺ through the T-tubule L-type Ca²⁺ channels
• this mechanism is not absolutely necessary for EC coupling in skeletal muscle but IS a requirement in cardiac muscle

• caused by mutations in SR ryanodine receptors
• this mutation causes no observable phenotype under normal conditions, however gaseous anesthetics (halothane) cause the mutant receptor to become more sensitive to cytosolic Ca²⁺
• normal Ca²⁺ release during a muscle contraction triggers massive & uncontrolled release of Ca²⁺ from the SR
• this causes muscle rigidity & a dramatic increase in muscle metabolic activity due to a large increase in ATP consumption in an attempt to return Ca²⁺ back into the SR via a usual ATP pump
• this causes increased oxygen consumption & elevated body temperature (hyperthermia) which can cause circulatory collapse & death if not treated

with dantrolene, a muscle relaxant, which lowers the Ca²⁺ affinity of the ryanodine receptor & blocks the uncontrolled release of calcium from the SR