Action potential and currents Flashcards
Define resting membrane potential + normal value
Difference in electrical charges btwn extra and intra¢ = -80-90mV
What are the most important ion gradients for RMP
large resting ion gradient
o Intra¢ [Na+] = 150mmol/L vs extra¢ = 25
o Intra¢ [K+] = 4mmol/L vs extra¢ = 150
- At rest, impermeable to Na+, partially permeable to K+ and Cl-
Relation of AP phases to ECG
- Phase 0 = QRS
- Phase 1 = J point
- Phase 2 = ST segment
- Phase 3 = T wave
- Phase 4 = electrical diastole
Phase 0 key events
RAPID DEPOL
* Opening of voltage gated Na+ channels
* Influx of Na+ =>membrane potential to +20-30mV = inward current (INa)
* Rapid upstroke = fully depolarize the ¢
Describe Na+ channel gates
2 gates
o M: activation gate => open when threshold of -65mV is reached
o H: inactivation gate => time dependent property of the channel = close channel after a certain time
Prevent any further exchange of Na+ during the rest of the AP
Phase 1 key events
EARLY REPOL
* When membrane potential reaches +30mV, triggers
o Closing of Na+ channels
o Slow opening of Ca2+ L-type
o Opening of voltage gated K+ channels = efflux of K+ = Ito
o Ca2+ activated Cl- current can also contribute to phase 1
More prominent phase 1
Better defined in atrial and Purkinje ¢ AP
Stronger in epicardium vs endocardium
Can cause J wave on ECG in R wave downslope
Phase 2 key events
PLATEAU
* While K+ still open => formation of outward currents larger IKS and smaller IKR
* Voltage gated Ca2+ channels (L type) also open around -30 to -35mV
o Slower in how they open vs K+ channels = Ca2+ influx (ICa-L)
Formation of a plateau: for every K+ out = Ca2+ in
o Plateau permits: small influx of Ca2+ => trigger larger release of Ca2+ => myocardial contraction
Cross bridge cycle and shortening of sarcomere
o Allows full movement of blood from that chamber before relaxation
If plateau is shorter and repolarization occurs beforehand = ejection of blood
* Final phase of plateau: membrane potential value => slowly 2nd to decr conductance of Ca2+ and incr K+
Phase 3 key events
- Determine AP duration, complex origin
o From initial depolarization, K+ currents activated w a delay (IKR, IKS, IKL)
IKR = major contributor
IKUR: K+ current in atrial myocytes responsible for shorter duration of AP
o Closure of Ca2+ channels in response to incr intra¢ [Ca2+]
o Inward current of Na+/Ca2+ exchanger becomes an inward current = Na+ entry
o Inward Cl- flow may contribute - Closing of Ca2+ channels = stops Ca2+ influx
- K+ channels still open = efflux of K+ => decr membrane potential = membrane potential decr to -90mV
Phase 4 key events
- Membrane potential back to resting values
o During diastole, activity of exchange systems maintain ionic balance
Which current maintain resting phase
Atrial, ventricular, His Purkinje ¢: value is mainly determined by conductance of K+ through IK1 channels
Atrial myocytes AP features
- Shorter => lesser contraction force
o decr inward Ca2+ flow - Short AP duration: rapid opening of IKUR → ↑K+ current
o Ultrarapid delayed rectifier current
o Lesser contraction force due to decr time for inward Ca2+ flow - Well defined phase 1: spiked and dome AP pattern
o ↑ ITo : early repolarizing current
Ventricular myocytes AP features
- Longer vs atrial potential but shorter vs Purkinje fibers
- Differ according to layers of ventricular wall
o Reflect different expression of ITO and IKS currents
Epicardial myo¢: doming shape, prominent phase 1
Mid myocardium myo¢: longer AP, prominent phase 1
Endocardial myo¢: intermediate duration, small phase 1
Purkinje AP features
- Longest AP: large rapidly rising AP
o ↓ internal resistance → favors rapid conduction
o Long duration: safety against re-entrant arrhythmia - Well defined phase 1: spiked and dome AP pattern
o ↑ ITo : early repolarizing current
Pacemaker cells AP features
Lower resting membrane potential: -40 to -70mV
* Absence of KIR2 channels responsible for IK1 current
* UNSTABLE MEMBRANE POTENTIAL = never goes to rest (because Na+ channels open at -60mV and repolarization takes the membrane to -60mV)
o Membrane/voltage clock: progressive decr of repolarizing currents at end of AP + initiation depolarizing currents
IF => activate HCN channels => Na influx
ICa-T & ICa-L => Ca influx
o Ca2+ clock: initiated by spontaneous release of Ca2+ by SR w ryanodine R => trigger Na influx and Ca efflux
* Pacemaker current IF: major contributor of spontaneous automaticity in SA and AV node
Steps of PM cells AP
- When membrane potential reach -60mV = opening of Na+ channel = slow influx of Na+
* Membrane potential ¬from -60mV to -40mV - When membrane potential reach -40mV
* Opening of fast Ca2+ channels (T type) = rapid influx
* Sharp rise in potential to around +10mV - Closing of Ca2+ channels and opening of K+ channels = efflux of K+
* Bring potential membrane back to -60mV
SA node automatic activity: which cells
P ¢
* Connected by each other by apposition of plasma membrane
* Coordination: transmembrane potential change almost simultaneously in all P¢
* Conductance from a dominant PM site => can shift in response to physiologic stimuli
Rate of spontaneous depolarization in SA node: 3 main factors
o Slope of phase 4: incr in slope => sooner reach of threshold => incr d/c rate
o Threshold potential: incr => delay onset of phase 0 => decr d/c rate and vice versa
o Membrane potential at initiation of phase 4: incr => easier to reach threshold => incr d/c rate
5 proposed PM currents to explain spontaneous depolarization in SA node
IK
IB
ICa-L and T
IF
o Safety factor: inhibition of 1 current leaves several others to carry depolarizing fct
- Spontaneous depolarization in phase 4
- Depolarization starts at -65mV => activation threshold -40mV => rapid depolarization initiate AP
o Slower upstroke
No fast Na+ current
o No plateau phase
Rapid onset of K+ repolarization from activation of delayed rectifier K+ current (Ik)
Normal spontaneous depol rates
- SA node: 60-180bpm
- AV node: 40-60bpm
- Purkinje fibers: 20-40bpm
Delayed rectifier K+ current (Ik)
- Major K+ current in PM ¢
- Alteration of its rate => important governor of AP pattern
- Activated when depolarization reach apex => contribute to repolarization
- Time dependent
Background inward current (IP or IB)
- Spontaneous inward Na+ current along [gradient]
- Remains when all other are blocked
- Role is controversial
Slow inward nodal Ca2+ current (ICa)
- Essential for PM activity
- Rising phases of AP
o Transient component (ICa-T): threshold -60 to -50mV
Open 1st (lower voltage)
o Long lasting component (ICa-L): threshold -40mV
Essential for the rapid upstroke
Affected by Ca2+ antagonists and B adrenergic blocks will slow but not arrest heart beat at clinical dosages
Inward current (If)
- Activation at lower membrane potentials = -90 to -50mV
o More negative than that usually found in P¢
o May be fully operative when SA node is hyperpolarized
Also named hyperpolarization-activated cyclic nucleotide-gated current (HCN) - N+ and K+ can carry => Na+ may be dominant