Flashcards in Cardiac Electrophysiology Deck (44)
4 types of biological electrical potentials
1. equilibrium potential (single ion, calculated from Nernst equation; idealized)
2. Gibbs-Donnan equilibrium (semi-permeable membrane with movable salts but immovable PRO/polyelectrolytes)
3. diffusion potentials (membrane permeable to 2+ ions)
4. epithelial membrane potentials (voltage between 2 dilute solutions separated by a membrane; kidney or GI)
approximate E (in mV) for Na+, K+, and Ca++
Na: +60 mV
K: -90 mV
Ca++: 120 mV
will raising or lowering K or Na concentration inside or outside of a cell cause depolarization or hyperpolarization?
depolarize: raising extracellular Na and K (increases inward Na, decreases outward K); more positive, less negative
hyperpolarize: raising intracellular Na and K (decreases inward Na, increases outward K); more negative, less positive
Ohm's law for electricity and relationship to biological ion channels
current is directly proportional to voltage
-biologically are non-Ohmic --> rectification
conductance of outward currents is greater than for inward currents, and voltage (and current) slopes upward nonlinearly (positive voltage has larger slope)
-also called "true"
conductance of inward currents is greater than for outward currents, and current (and voltage) plots slope downard nonlinearly (negative voltage gives higher slope)
-also called "anomalous"
is the K+ channel inward or outward rectifier? (more specifically, the iK1)
it can be both!
iK1 is an inward/anomalous rectifier (for resting membrane potential)
-when hyperpolarized, or at rest, the conductance is high b/c voltage is negative (positive efflux of K+)
-when depolarized, the conductance is lower
molecular structure of mammalian K+ channel
4 identical polypeptide subunits
-transmembrane domain forms pore that allows ions to cross membrane
-selective filter VS ions other than K+
how do ions move through open channels?
in single file electrodiffusion
-so more than 1 ions may occupy a channel, but don't pass each other in transit
action of Ca++ channel blockers
reduce HR and contractility of heart
-lower CO and BP
action of ACE inhibitors
block conversion of angiotensin I to II
-relaxes smooth muscle, decreased TPR and BP
are the Na+ and Ca++ channels inward or outward rectifiers?
outward/real rectifiers (conductances are low if hyperpolarized)
-undergo 3 state models of closed (resting) --> open --> closed (inactive) --> closed (resting)
-both time and voltage dependent
what happens if the initial resting potential more depolarized than usual?
some channels are in inactivated state, so ensuing action potential is smaller and has slower upstroke than normal
what happens if stimulating voltage to threshold has slower upstroke than usual?
some channels will inactivate, so ensuing action potential is smaller and has slower upstroke than usual
-important in AV node of heart where arrhythmias occur
are there voltage-gated outwardly rectifying K+ channels?
yes, these are active during repolarization of action potentials
-open when transmembrane voltage becomes positive
-conductance is higher when depolarized than hyperpolarized, currents are outward
how does the delayed rectifier K+ channel activate/deactivate?
activate: time delay (finite duration for depolarization)
inactivates: ball and chain mechanism (spontaneous via peptide domain attached to beta-subunit on cytoplasmic side)
-has larger conductance at positive depolarized than negative hyperpolarized
what happens if the peptide domain attached tot he beta-subunit on cytoplasmic die of delayed outward rectifier K+ channel is cleaved?
if peptide is experimentally cleaved by proteolytic enzyme, inactivation property is lost, and channel stays open
how do APs in SA node, atrium, AV node, bundle of his, purkinje network, and ventricle differ?
atrium, bundle, Purk, and ventricle have APs with Na-dependent upstrokes, Ca-dependent plateaus, and K-dependent repolarizations
SA and AV node have smaller Ca-dependent upstrokes, and K-dependent repolarizations, with no Na contribution or plateaus
-SA has pacemaker potential and spontaneously ramp depolarization for heart rhythm
differences between skeletal muscle and cardiac muscle action potenials
1. duration of skeletal muscle is a few milliseconds, cardiac have plateau lasting 300-400 milliseconds (except for SA and AV node)
2. phases 1/2 of cardiac don't have counterparts in nerves
3. repolarization is monophasic in skeletal (K+), but triphasic for cardiac (slow Ca++, delayed K+, inward K+)
what are the largest action potentials of the heart? and what are the resting potential, overshoot, and amplitude?
Purkinje fiber APs
-resting potential -90mV
-overshoot +30 mV
-amplitude of AP >120 mV
ionic currents responsible for Purkinje fiber AP
phase 0 - upstroke; fast inward Na+ current that rapidly inactivates (iNa)
phase 1 - transient repolarization; transient outward K+ currents (it01, it02)
phase 2 - plateau; slow outward K+ currents (iKr, iKs, iKCa) and slow inward L-type Ca current (iCaL) that all slowly inactivate
phase 3 - repolarization; delayed outward rectifier potassium currents (iKr rapidly activating and iKs slowly activating)
phase 4 - resting potential; inward rectifier potassium currents (iK1)
difference between L-type Ca channels and T-type Ca channels
L: opens due to Na+ channels yielding depolarization, b/c L threshold is more positive than Na+ threshold
-large size, for SA/AV conduction, excitation-contraction coupling
T: opens transiently upon depolarization, but current is small and overshadowed by large Na+ current
-important for contributing to generation of pacemaker currents in SA node (but not AV node)
-small size, with proliferative signaling
both function for contraction
SA node action potentials
pacemaker activity (60-100 APs/minute)
phase 0 - rapid depolarization (rising) phase due to iCa via voltage-dependent, L-type channels
phase 3 - slower repolarization (falling) phase due to inactivation of iCa, plus activation of delayed, voltage-dependent iK
phase 4 - slow, ramping depolarization b/c of activation of if (pacemaker current)
what causes SA node pacemaker activity?
from interaction between iCat, iK, and if (funny, pacemaker current)
-if has net inward current that activates in response to hyperpolarization (instead of depolarization), and has both inward (Na) and outward (K) component
3 mechanisms that can slow the SA node pacemaker
1. decreased rate of diastolic hyperpolarization
2. diastolic hyperpolarization
3. increased thresh-hold
ANS regulation of SA node
regulated by neuronal input
-parasympathetic inhibition via vagal brake
--ACh released at heart to M2 (metabotropic) receptor
--activation of Gi decreases [cAMP]
--NE released at heart to beta1 (metabotropic)
--activation of Gs activates adenylyl cyclase to increase [cAMP]
mechanisms of action for vagal brake
reduce phase 4 steepness by:
-decreasing inward if and iCaT
-increasing outward KAch
mechanisms of action for sympathetic stimulation for SA node
increasing phase 4 steepness by:
-increasing inward if and iCaT
-decreasing outward KAch
-threshold of iCaL is at more negative value
cardioselective beta blocker effects on heart
block beta1 receptors to cause bradycardia (atenolol, propranolol)