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What is normal resting membrane potential?
-80 to -90 mV
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Changes in trans-membrane polarity are mostly due to... (2)
opening of ion channels, movement of ions across the cell membrane
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Depolarization means the trans-membrane potential is...
less negative/closer to zero.
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What are the phases of cell membrane potentials?
- phase 0- depolarization
- phase 1- brief repolarization (ignore)
- phase 2- plateau
- phase 3- repolarization
- phase 4- resting membrane potential
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What is conductance (g)?
permeability of the membrane to a certain molecule/ion
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Conductance is altered by... (4)
trans-membrane voltage (voltage-gated channels), time after opening (time-dependent channels), extracellular ion concentrations, ligands (ligand-gated channels: Ach and NE)
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Inside of cell has very high ____, which is very low outside the cell; therefore, this ion moves out of the cell, along its concentration gradient, until...
K+; it is eventually held in the cell by electrical force of negatively-charges proteins (which themselves are trapped inside because of their large size).
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Resting membrane potential in cardiomyocytes is mainly related to the _____________ and _____________.
K+ conc and conductance of this ion
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During phase 4, resting membrane potential is ___________, and ion distribution is replaced to normal by the ____________.
relatively constant; Na+K+ATPase pump (removes 3Na+ and replaces 2K+)
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Sodium channels are _______-voltage operated channels, which means...
fast; they are activated at a threshold membrane potential and rapidly close after opening (time-dependency).
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How are Na+ channels regulated?
voltage-gated and time-dependent
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What is the purpose of fast Na+ channels?
depolarization (Phase 0) of muscle cells and Purkinje cells
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What is the Vaughan Williams anti-arrhythmic drug Class I? What drugs are in this class?
Sodium channel blockers; IA- procainamide, quinidine; IB- lidocaine, mexiletine; IC- flecainide, propafenone
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What are some clinical issues that are related to ion channels of the heart? (3)
- inherited channelopathies: cause of SCD- altered repolarization
- heart disease: can affect channel function and lead to heart rhythm disturbances
- Ionophores: coccidiostat feed additives- preferentially transport ions across cell membranes- cause myocardial injury if given in too high dose or if accidentally ingested by horses or camelids.
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What forces keep K+ in the cell? (2)
negatively-charged proteins that are too large to leave the cell, high Na+ conc outside the cell
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What forces keep Na+ out of the cell? (1)
membrane is relatively impermeable to Na+
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How does hyperkalemia cause bradycardia?
when you have high extracellular K+ compared to intracellular, transmembrane voltage becomes less negative, effectively bypassing the membrane potential at which Na+ channel open--> Na+ don't open--> atrial mm. are inexcitable--> brady
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What are the purposes of the Ca2+ channels of the heart?
contraction of cardiac and smooth mm. myocytes, depolarization of pacemaker cells in SA and AV nodes
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What are the 2 types of Ca2+ channels in the heart?
T-type (transient) channels that are activated at more negative potentials, L-type (long-lasting) channels that are ligand-operated (catecholamines)
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What is the Vaughan Williams anti-arrhythmic drug Class IV? What drugs are in this class?
Calcium channel blockers- directly block L-type channels; Diltiazem, Amlodipine
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What is the Vaughan Williams anti-arrhythmic drug Class II? What drugs are in this class?
beta-blockers that indirectly decrease Ca2+ influx by modulating opening/closing of L-type channels; "lol" drugs (end in "-lol")
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What is the purpose of K+ channels of the heart?
repolarization by allowing K+ to move out of the cell, along its conc gradient
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How are K+ channels regulated?
voltage and ligand-operated
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Describe the ligand-dependent operation of K+ channels.
Vagal (parasympathetic) Ach opens a specific K+ channel, slowing depolarization and enhancing repolarization in pacemaker cells (in supraventricular tissues- atria, SA node, AV node)
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K+ channels are the rate of repolarization contribute significantly to the ____________ of the cell, which is...
refractory period; time period when the cell cannot be re-stimulated after depolarization.
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Why is inhomogeneity of RPs dangerous?
facilitates development of fragmented spread of current across the ventricles, leading to myocardial fibrillation
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What is the Vaughan Williams anti-arrhythmic drug Class III? What drugs are in this class?
block ion movement across K+ channels, prolonging repolarization; sotalol, amiodarone
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Cell repolarization correlates to the __________ on EKG; _______ is lengenthed by drugs that prolong this.
ST interval; RP
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What causes depolarization of slow current Ca2+ channels in the pacemaker cells?
slow inward current of Ca2+--> drifting upward toward action potential--> spontaneous depolarization
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Why isn't there really a Phase 2 plateau with slow current Ca2+ channels?
cells in the SA and AV nodes are not contracting muscles, their only purpose to si RAPIDLY conduct current
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What are the EKG effects of hyperkalemia? (4)
bradycardia from depression of SA node activity, inexcitability of atrial cardiomyocytes leading to absence of P waves, depressed cell-to-cell depolarization of ventricles leading to depression of phase 0, large T waves due to opening of K+ channels and more rapid repolarization
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What part of the EKG lead corresponds to repolarization?
T wave (ie. more rapid repolarization with hyperK+--> taller/more tented T wave)
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What is occurring during the plateau phase 2?
Ca2+ is entering the myocytes to stimulate muscle contraction
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What are the insulators of the atria and ventricles, and what are the chambers connected by?
cardiac valves and fibrous connective tissues are insulators; chambers are connected electrically by microscopic conduction pathway, AV node and Bundle of His
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What part of the EKG lead corresponds to atrial depolarization?
P-wave
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What part of the EKG corresponds with current spread across the AV node?
PQ interval
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What part of the EKG lead corresponds with sequential depolarization of the ventricular myocytes?
QRS complex
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What is the distribution of Ca2+ across the cell membrane?
intracellular Ca2+ is low compared to extracellular; Ca2+ does not contribute to the transmembrane potential b/c most of the intracellular C2+ is sequestered in the sarcoplasmic reticulum
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What is the distribution of Na+ across the cell membrane?
intracellular Na+ is low compared to extracellular
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Define an activated membrane ion channel.
once a specific ion channel is open or activated, ions can flow through the channel by their concentration gradient
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Describe how the process of Na+ channels opening and depolarization occurs.
spontaneous depolarization of pacemaker cells in the SA node--> current flow across gap junctions--> depolarization of atrial and ventricular muscle cells and specialized conduction cells of the His-Purkinje system
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_____________ have a prominent affect on L-type Ca2+ channels, increasing the probability of opening and Ca2+ influx; this facilitates __________ and generation of a ___________.
Catecholamines (sympathetic NS); depolarization; faster HR
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High vagal tone __________ the refractory period of atrial muscle cells .
shortens
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What is the purpose of the Na+K+ATPase pump?
maintain the negative intracellular potential (during phase 4) while also re-establishing the normal partitioning of ions of each side of the membrane.
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Normally, the ________ is the pacemaker of the heart; the __(2)__ serve as back-up or escape pacemakers should the primary fail.
SA node; AV node and His-Purkinje cells [subsidiary pacemaker cells]
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Both NE and Ach enhance ____________ and _____________ the SA nodal membrane; however, NE, the activation of the ___________ causes fuller opening of the ____________, promoting more rapid ___________; the opposite occurs with vagal Ach.
repolarization; hyperpolarize; funny pacemaker current; long-lasting Ca2+ channels; depolarization
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What is ventricular escape?
Ventricular escape beat is a self-generated electrical discharge initiated by, and causing contraction of, the ventricles of the heart; normally the heart rhythm is begun in the atria of the heart and is subsequently transmitted to the ventricles.
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