Action potential

Question 1

Resting membrane potential

Answer 1

• Difference in electrical charge btw intr/extracell space
  o At rest: cell membrane is impermeable to Na+, partially permeable to K+/Cl-
   Resting transmembrane potential = -80 to -90mV
   True resting transmembrane potential is absent in PM cell → constant depol state
• Lowest = -70 to -50mV
• Depend on channel expression
  o Na+/K+ pump maintain low intracell [Na+], ↑ [K+]

Question 2

Threshold potential

Answer 2

trigger action potential
o Nodal cell = -40mV
o Purkinje/working myocardium cell = -65 to -70mV

Question 3

Phases of fast response action potential + which cells

Answer 3

• Phase 0: rapid depolarization
• Phase 1: early repolarization
• Phase 2: plateau
• Phase 3: final
• Phase 4: resting phase

Myocytes

Question 4

Phase 0 events and channels involved

Answer 4

o Rapid ↑ of transmembrane potential to peak +30mV
 INa current: rapid Na+ influx through voltage gated Na+ channels
* m gate opening at -65mV
 ↓ membrane permeability to K+

Question 5

Phase 1 events and channels involved

Answer 5

o Brief period of repol to 0mV
 ITo current: K+ efflux
 Stronger in epicardium vs endocardium
 Responsible for J wave on ECG
 Expression of this channel not fully present until 4-5 mo/o
o If ↑ → prolong AP vs if ↓ → shorten AP duration
o Membrane potential at the end of phase 1 determine magnitude of Ca2+ current

Question 6

Phase 2 events and channels involved

Answer 6

o Opening of long lasting Ca2+ channels (L type) at -10mV
 ICa-L: Ca2+ influx
* Trigger release of larger Ca2+ amount by SR → trigger myocardial contraction
* Inactivated after 100-150ms to prevent constant state of depol
 IKs + IKr: K+ efflux → compensate Ca2+ influx
o Gradual ↓ membrane potential due to ↓ conductance to Ca2+ and ↑ to K+

Question 7

Phase 3 events and channels involved

Answer 7

o Rapid ↓ in transmembrane potential from 3 K+ currents
 IKs: slow delayed rectifier
 IKr = MAJOR CONTRIBUTOR: fast delayed rectifier
 IK1
 IKur → only in atrial myocytes
* Responsible for shorter AP duration

Question 8

Phase 4 events and channels involved

Answer 8

o Resting values of membrane potential
 Mainly determined by high K+ conductance through IK1 channels
o Intra [ions] restored by ionic pumps (Na/K+, Ca-ATPase) and exchangers (Na/Ca)

Question 9

Overshoot phase

Answer 9

transition from – to + membrane potential
 h gate closure: time dependent property of Na+ channels
* Remain closed until resting membrane potential

Question 10

Phases of slow response action potential: major difference + which cells

Answer 10

SA and AV nodes

NO phase 1

Phase 4: less negative membrane potential
 Absence of Kir2 channel → responsible for IK1 current

Stable resting potential is not present

Phase 0: depend on Ca2+ current (ICa-L)
 Absence of voltage gated Na+ channels
 Threshold -40mV
 Slower upstroke, lower amplitude

Question 11

PM action potential: spontaneous depol

Answer 11

o Stable resting potential is not present → slow depol starts after the end of preceding AP
 Membrane/voltage clock:
* Closure of K+ channels → ↓ repol currents
* Repolarizing currents: If from HCN channels (Na+ influx), ICa-T, ICa-L (Ca2+ influx)
 Ca2+ clock: spontaneous release of Ca2+ from SR through ryanodine R
* Na+ influx and Ca2+ efflux in 3:1 ratio

Question 12

Spontaneous automaticity of PM cells: normal conditions

Answer 12

o Normal conditions: rate of d/c ↑ in SA node PM  → dominant PM
 SA node: 70-160bpm
 AV node: 40-60bpm
 Purkinje fibers: 15-40bpm

Question 13

Overdrive suppression

Answer 13

↑ activity of Na/K ATPase → hyperpolarization
 Prolong time to reach threshold

Question 14

Rate of depolarization is modulated by

Answer 14

 Slope of phase 0: ↑ slope → sooner reach of threshold → ↑ d/c rate
 Threshold potential: ↑ value (more positive) → delay onset of phase 0 → ↓PM d/c rate
 Membrane potential at phase 4: ↑ value →easire to reach threshold → ↑d/c rate

Question 15

Transmural dispersion of action potential

Answer 15

Different AP morphology/duration: reflect expression of ITo/IKs
* Epicardial myocytes: ↑ # ITo
o Prominent phase 1
o Doming shape
* Mid myocardium (M cells): ↓ # ITo, ↓ # IKs
o Visible phase 1
o Longer AP duration (prolonged phase 2 → ↓ # IKs)
* Endocardial myocytes: almost no ITo
o Small phase 1
o Intermediate AP duration
* Electrical heterogeneity → can serve as substrate for arrhythmias (reentry)

Question 16

Relation to surface ECG

Answer 16

Phase 0  QRS
Phase 1  J point
Phase 2  ST segment
Phase 3  T wave
Phase 4  electrical diastole

Question 17

Depolarization starts

Answer 17

endocardium → epicardium
o Propagation from endo to epi is approx. 30ms

Question 18

Reporalrization starts

Answer 18

epicardium → endocardium
o Ascending limb of T wave = epicardial myocytes
o Descending limb = endocardial myocytes

Question 19

Electrical properties of myocardium

Answer 19

Excitability
Automaticity
Refractoriness
Conduction velocity

Question 20

Excitability def

Answer 20

ability of cell to generate AP
o Depends on Na+ channels availability in response to stimulus

Question 21

Automaticity def

Answer 21

ability to spontaneously depolarize
o SA node + subsidiary PM
o Subsidiary PM are latent, inhibited by faster SA node rate of depol → overdrive suppresion

Question 22

Refractoriness def

Answer 22

period of time where myocytes are unexcitable (phase 0 → 3 due to Na+ channel inactivation)

Question 23

Refractory periods

Answer 23

o Effective refractory period: phase 0 → repol (QRS → end of T wave)
 Appropriate stimulus cannot provoke AP
 -50mV or less: all Na+ channels are inactivated

o Relative refractory period: mid phase 3 → end phase 3
 Progressive reactivation of Na+ channels when potential reach -50mV
 Response to intense stimulus is possible
* ↓ upstroke velocity (low # of Na+ channels available)
* Slower impulse conduction

o Total refractory period = effective + relative

Question 24

Supernormal excitability

Answer 24

short period after relative
 Subthershold stimulus can initiate AP
 Period where membrane potential is close to threshold

Question 25

Effect of HR on RP

Answer 25

 ↓ cycle length/↑HR: shorter and vice versa

Question 26

Conduction velocity def

Answer 26

ability to propagate an impulse
o Fast response fibers: α to intensity of Na+ current in phase 0 and mx diastolic value
 Slope of phase 0: rate of change in membrane potential
* ↑ → ↑ conduction velocity
 Value of resting membrane potential: determine # of Na+ channel available
* -90mV: 100%, -75mV: 50%, -40mV: 0%
 Other factors
* Cell diameter
* # of intercalated discs
* Type of connexins in gap jcts