Excitability Of Ventricular Cells

Front 1

Phases of Ventricular Cell AP and names

Back 1

Phase 4 - rest/diastole
Phase 0 - depolarization/upstroke
Phase 1 - early repolarization
Phase 2 - plateau
Phase 3 - repolarization

Front 2

Phase 4 channels and permeability

Back 2

Phase 4 (rest/diastole) – dominated by KIR channel (producing IKr current) & PK. More permeable to Na then other cells.

Front 3

Phase 0 channels and permeability

Back 3

Phase 0 (upstroke of AP) – ↑ in PNa

Front 4

Phase 1 channels and permeability

Back 4

Phase 1 (early repolarization) – transient ↑ PK & ↓PNa (channel inactivation)

Front 5

Phase 2 channels and permeability

Back 5

Phase 2 (plateau) - ↑ PCa (VGCa channels) & ↓PK (indirectly V, dependent Mg2 blocks channel)

Front 6

Phase 3 channels and permeability

Back 6

Phase 3 (repolarization) - ↓PCa (channel inactivation) & ↑PK (voltage gated “delayed rectifiers” and then ↑↑PK (Mg2 removeed and IK1 restored)
When IK1 is restored so is resting membrane as in Phase 4.

Front 7

Ventricular Cells relative permeability

Back 7

At rest (phase 4) – the Na permeability is higher and thus Na/K ATPase density is higher.
Generally cells at rest have low ion permeabilities requiring less E at rest. However, Cardiac muscle has high ion permeabilities at rest. Again like the resting situation cardiac muscle is opposite of the general rule. During activation most cells have increased ion permeability. Cardiac muscle has decreased ion permeabilities during activation = this allows sustainable high rates of contraction without the loss of K gradient. K+ efflux is spared.

Front 8

AP diagram in Ventricular Cell

Back 8

Front 9

Significance High K permeability in cardiac function

Back 9

10X fold higher PK results in more stable resting EM. This means ↓ risk for arrhythmias leaving the ventricles a slave to the pacemaker cells.

Front 10

NE /Epinephrine affect on ventricle AP

Back 10

Shortens ventricular AP

NE released from sympathetic fibers resuts in activation of PKA. The kinase (P) Ca-L(voltage gated), KR (rapid), KS(slow) channels.


PCa is altered after the initial slope. Reason for the same initial is that it is a voltage gated channel and thus dependent on the same voltage change.
Sympathetic (NE) results in 25-35% ↓ AP time BUT 50-75%↓↓ time betw/ AP.

Front 11

Epi/NE affect on Ventricle AP

Back 11

Front 12

Refractory Periods Diagram

Back 12

Front 13

Order of the 3 refractory periods

Back 13

Absolute refractory period (<50% Na available)

Relative refractory period (<95% Na available) - larger stimulus produces a smaller than normal propagated AP

Supranormal period - slightly smaller stimulus produces normal propagated response

Full recovery time

Front 14

Normal QT interval

Back 14

QT interval (0.12 – 0.2 seconds) – measures time beginning ventricular depolarization to end of ventricular repolarization

Front 15

Prolonged QT

Back 15

Therefore a prolonged QT represents a slow ventricular depolarization-repolarization cycle. Arrthymias are common at elevated HR. Additionally, at elevated HR, ventricular filling ↓ as well as CO ↓. This is because less time is spent in refilling because the contraction time cannot decrease and heart is being told to ↑HR leaving only the PR interval to decrease (P wave + PQ segment).

Front 16

Common cause prolonged QT syndrome

Back 16

Genetic Mutations in

1. Delayed rectifier K channels
 Delayed activation (90% of cases)
 ↓ probability of opening
 ↓ sensitivity to PKA modulation
2. Voltage gated Ca channels
3. Voltage gated Na channels