Cardiac Cellular Electrophysiology

Question 1

what is the specialized conduction system

Answer 1

histologic components of the heart that are responsible for conducting electrical impulses throughout the cardiac muscle for rhythmic contraction

Question 2

what is the path of current conduction in the heart

Answer 2

SA node
internodal tracts
AV node
penetrating bundle of His
L and R bundle branches
purkinje fibers

Question 2

what makes up the nodal tissue

Answer 2

sinoatrial and atrioventricular nodes

Question 2

characteristics of nodal action potentials

Answer 2

SLOW - spontaneously generated

depolarization is based on inward CALCIUM current

Question 2

sinoatrial node

Answer 2

fast nodal tissue
generates APs to set the rhythm of contraction (pacemaker)

Question 2

atrioventricular node

Answer 2

slow nodal tissue
(does NOT pacemake unless SA node fails)

conducts signal across from atrium to ventricle

Question 3

what makes up the non-nodal tissue

Answer 3

myocytes (atrial and ventricular)
bundle branches
Purkinje fibers

Question 4

characteristics of non-nodal action potentials

Answer 4

FAST - cells are waiting to be stimulated by the AP generated by SA node

propagates AP via gap junctions for rapid spread of the signal

depolarization is based on inward SODIUM current

Question 5

excitation contraction coupling

Answer 5

depolarization of the cell leads to opening of Ca channels –> Ca influx –> release of Ca from SR stores –> high intracellular Ca –> binds troponin C on actin –> contraction

Question 6

are cell membranes polarized or unpolarized

Answer 6

polarized - membrane potential changes during the cardiac cycle

caused by varied conductance of ions through ion channels

Question 7

conductance

Answer 7

movement of charge across membrane that is dependent on ion channels opening and closing

high conductance = high ion movement across membrane

Question 8

what does ion conductance depend on

Answer 8

VOLTAGE

also:
- ligand binding
- NE/epi concentration
- ion concentration (gradients)

Question 9

phases of the non-nodal action potential

Answer 9

phase 0: depolarization
phase 1: early/rapid repolarization
phase 2: plateau
phase 3: repolarization
phase 4: resting membrane potential

Question 10

resting membrane potential (RMP)

Answer 10

negative membrane potential maintained during phase 4 (diastole)

Question 11

RMP of nodal cells

Answer 11

-50 to -60

slow drift - MP slowly increases to threshold due to funny currents

Question 12

funny currents

Answer 12

I(f)

special Na and K channels in nodal cells open in response to the hyperpolarization that occurs in phase 3 of the cardiac cycle –> causes slow influx of positive ions –> membrane potential slowly increases to reach threshold –> once threshold is reached an action potential is generated

allows nodal cells to be able to spontaneously generate action potentials without a stimuli

Question 13

RMP of non-nodal cells

Answer 13

-80 to -90

does NOT slow drift - has a stable resting membrane potential

Question 14

how do non-nodal cells maintain a negative resting membrane potential

Answer 14

leaky K channels

increases extracellular K –> triggers Na/K pump –> 2K in, 3Na out –> RMP remains negative

Question 15

how do non-nodal cells depolarize

Answer 15

NOT SPONTANEOUS

AP generated by nodal cells –> spreads to non-nodal cells –> opens Na channels –> depolarizes cell –> AP spreads through gap junctions to adjacent cells

Question 16

what ion drives nodal cell depolarization

Answer 16

calcium

Question 17

what ion drives non-nodal cell depolarization

Answer 17

sodium

Question 18

threshold potential

Answer 18

Na channels: -60 to -70 mV

lowest membrane potential that triggers enough voltage Na or Ca channels to opens

yields an “all or nothing” response that generates an action potential

Question 19

absolute refractory period (ARP)

Answer 19

period following depolarization of a cell during which NO subsequent stimulus arriving at the cell can cause another depolarization

protective mechanism that prevents multiple, compounded APs

occurs during phase 1 and 2

Question 20

effective refractory period (ERP)

Answer 20

short period after ARP during which a STRONG subsequent stimulus arriving at the cell can cause another depolarization

occurs at the beginning of phase 3

Question 20

relative refractory period (RRP)

Answer 20

period after ERP during which a moderate subsequent stimulus arriving at the cell can cause another depolarization

occurs the remainder of phase 3

**vulnerable period - stimulus during peak of T wave can induce ventricular fibrillation

Question 21

class III antiarrhythmics

Answer 21

K channel blockers

prolong refractory period to reduce vulnerability to premature depolarization

ex. sotalol and amiodarone

Question 22

are sodium channels/current located in nodal or non-nodal cells

Answer 22

non-nodal cells only

Question 23

function of sodium current

Answer 23

rapid depolarization (phase 0) and spread of conduction in myocytes and Purkinje fibers

Question 24

mechanism of sodium channels

Answer 24

FAST - opens in response to AP from adjacent cell and closes quickly after

opens at -60 to -70

Question 25

if RMP is decreased (less negative), how is Na conductance affected

Answer 25

decreases Na conductance

Na channels are less excitable –> slows phase 0 down

Question 26

if RMP is increased (more negative), how is Na conductance affected

Answer 26

increases Na conductance

Na channels are more excitable –> speeds up phase 0

Question 27

what class of drugs targets Na channels

Answer 27

class I antiarrhythmics (IA, B, C)

ex. lidocaine - blocks Na channels to decreased excitability of cells and slow conduction

Question 28

are calcium channels/current located in nodal or non-nodal cells

Answer 28

both

nodal: slows depolarization (phase 0) for regular rhythm

non-nodal: allows Ca influx for contraction and plateau (phase 2)

Question 29

types of Ca channels/currents

Answer 29

L type and T type

Question 30

T-type calcium channels

Answer 30

present in nodal cells only

transient/tiny burst; opens at -50 to -60 (more negative MP)

initiates depolarization (phase 0) in nodal cells

Question 31

L-type calcium channels

Answer 31

present in nodal and non-nodal cells

longer lasting/later; opens at -30 to -40 (more positive MP)

nodal: minor effect; propagates depolarization (phase 0)

non-nodal: important for Ca influx for contraction and plateau

Question 32

what class of drugs targets Ca channels

Answer 32

catecholamines - increases HR/conduction/contractility

class IV antiarrhythmics - decreases HR/conduction/contractility by blocking L-type Ca channels

class II antiarrhythmics (beta blockers) - decreases HR/conduction/contractility by reducing phosphorylation of Ca channels to indirectly block L-type channels

Question 33

function of potassium channels/current

Answer 33

keep or return cells to resting membrane potential

Question 34

types of K channels/currents

Answer 34

I(KI): leaky K channels that maintain RMP in myocytes

I(KR) and I(KS): rapid (R) and slow (S) channels that allow repolarization (phase 3); triggered to open by depolarization

Question 35

what class of drugs target potassium channels

Answer 35

catecholamines: increase I(KR) and I(KS) to increase rate of repolarization

ADP: (indicates energy depletion); accelerates repolarization to shorten overall AP duration to conserve energy –> reduces contractility

hyperkalemia: reduces leaking in phase 4 –> depolarizes membrane –> increases k conductance to accelerate repolarization

Question 36

sympathetic effects on nodes

Answer 36

B adrenergic receptors

stimulates I(f), I(CaT), I(CaL), I(K) to increase HR and conduction speed

Question 37

parasympathetic effects on nodes

Answer 37

acetylcholine

inhibits SNS effects and activates I(Kach) –> hyper polarizes –> prolongs time for funny current to bring membrane potential to threshold –> decreases HR and conduction speed