Chapter 2: Characteristics of Cardiac Muscle Cells

Question 1

List 3 differences between cardiac and skeletal muscle cell action potentials

Answer 1

• can be self-generating
• conduct action potential from cell to cell
• long duration action potential

Question 2

What are the 3 states ion channels can be in? When do these 3 stages occur in the fast Na channel during a fast-response action potential?

Answer 2

closed - activation gate closed
open - inactivation and activation gate open
inactivated - inactivation gate closed

• initially Na channel is closed - when reaching the threshold potential the activation gate opens
• for a few miliseconds Na can enter the cells - then the inactivation gate closes

Question 3

Explain what the potassium equilibrium potential means, what is the name of the equation used to determine the equilibrium potential of an ion?

Answer 3

potassium equilibrium potential is the transmembrane potential at which the potassium moved out of the cells to a degree where IC and EC K+ cc are equal. Usually around minus 90

Nernst equation

Question 4

List the different phases and associated ion movements/currents during a fast-response action potential

Answer 4

• phase 4 - potassium permeability high, resting membrane potential close to the potassium equillibrium potential, rectifying K channel, K moves out of cell, making the transmembrane potential negative
• phase 0 - fast Na channels open with inward Na movement - transmembrane potential becomes positive (iNa)
• phase 1 - brief outward-going potassium current (iT0) open causing an initial drop in the transmembrane potential, following by a sustained reduction in K+ permeability
• phase 2 - L-type Ca channels open, with inward Ca current, creating a plateau positive transmembrane potential
• phase 3 - delayed rectifying K channels open, K moves out of cell and reestablishes the negative resting membrane potential

Question 5

List the different phases and associated ion movements/currents during a slow-response action potential

Answer 5

• phase 4 - funny current with inward Na and Ca movement via HCN channels + decrease in K permeability (less potassium can move out of the cell) –> causing a slow change in the transmembrane potential to more positive, i.e., autonomically reaching the threshold potential
• phase 0 - L-type Ca channels - Ca movement in - positive transmembrane potential
• no phase 1 or 2
• phase 3 - delayed rectifying K channels open and cause outward movement of K –> regaining negative transmembrane potential

Question 6

What are other names for the unstable resting potential in slow-response action potentials?

Answer 6

pace maker current
phase 4 depolarization
diastolic depolarization
pacemaker potential

Question 7

during a fast-response cardiac action potential, what are the 3 phases of responsiveness and when do they occur?

Answer 7

• absolute refractory period- during most of the action potential - cannot be stimulated
• relative refractory period - cells can be reexited only by a larger-than-normal stimulus
• supranormal period/vulverable period - near the end of the aciton potential - transiently hyperexitable immediately after the action potential

Question 8

Explain the funny current

Answer 8

HCN channels increase permeability of Ca and Na into the cell during the diastolic depolarization phase of slow-response cardiac cells (pacemakes cells)
at the same time the K permeability decreases

net effect: transmembrane potential moves slowly towards a less negative value until reaching the threshold potential

Question 9

What family of channels does the channel maintaining the funny current belong to?

Answer 9

HCN
non-selective cation hyperpolarization-activated, cyclic nucleotide-gated channels

Question 10

Explain the different effects of moderately elevated versus severely elevated extracellular potassium concentrations on the action potential of cardiac myocytes

Answer 10

moderately high K cc disables the fast Na channels - cells become slow-response cells

very high K cc disables both fast and slow-response - asystole

Question 11

What are the different components of intercalated discs of myocardial cells?

Answer 11

intercalated discs = end-to-end cell connections between neighboring cells

• desmosomes: firm mechanical attachements between cell membranes –> build by proteins called adherins (cadherin)
• gap junctions: low -resistance electrical connections –> build by proteins called connexin

connexin can be phosphorylated or dephosphorylated – affects conduction velocity

Question 12

How is conduction velocity of the heart defined and what are its 3 determining variables?

Answer 12

conduction velocity - how fast action potential can move from cell to cell - i.e., how fast it can propagate through a region of cardiac tissue

determined by:
* size/diameter of the muscle fiber involved
* intensity of the depolarizing current
* conductance of the cells, i.e., capacities/resistive properties

Question 13

What arm and leg does lead II correspond to?

Answer 13

right arm
left leg

Question 14

What determines the intrinsic HR generated by the SA node (i.e., no autonomic nervous system effects)

Answer 14

the funny current, i.e., the spead of spontaneous diastolic depolarization - usually 100 beats per minute

Question 15

Explain how vagal stimulation slows the heart rate

Answer 15

vagus nerve –> parasympathetic fibers –> release acetylcholine –> SA nodal cells –>
increases K permeability and decreaes HCN channel permeability (less permeable to Ca and Na) –> funny current decreased

2 effects:
* initial hyperpolarization (more negative resting membrane potential
* slower rate of spontaneous depolarization

Question 16

Explain how an increase in sympathetic tone increases the heart rate

Answer 16

norepinephrine –> SA node –> increase Ca and Na permeability through HCN –> increases diastolic depolarization and hence heart rate

Question 17

Why can giving IV Ca-gluconate cause a decrease in the heart rate?

Answer 17

high EC Ca++ cc –> less negative/ “higher” threshold membrane potential

Question 18

How can the autonomic nervous system affect the duration of the PR interval?

Answer 18

by reducing or increasion the conduction velocity of the AV node

epinephrine –> dromotropic effect: increased conduction velocity

Question 19

Describe the parts of a sarcomere

Answer 19

paralllel interdigitating thick and thin filaments arranged in serial units
myosin
* thick filaments
* long straight tail with 2 globular heads with each containing an ATP-binding site and an actin-binding site
* light chains loosely associated with myosin heads - their phosphorylation modulates/regulated actin binding
actin
* thin filaments
* 2-alpha-helical strands of polymerized subunits (g-actin)
* extending from the Z-lines

Question 20

What are the 2 proteins bound to the sarcomere’s thin filaments and what do they comprise off + what is their function?

Answer 20

• tropomyosin: regulatory fibrous-like protein, lays in the groove of the actin alpha-helic, prevents actin to bind to myosin when at rest
• troponin - troponin T - connection to tropomyosin, troponin C - calcium binding site to cause troponin I to leave actin to stop blocking it from binding to myosin

Question 21

Describe titin

Answer 21

macromolecule extending from the Z line to the M line in the middle of each sarcomere

contributes to the passive stiffness of cardiac muscle cells

its phosphorylation can alter passive elastic properties of the muscle

Question 22

Describe in detail the steps of sarcomere contraction during cardiomyocyte excitation

Answer 22

action potential phase 2 - Ca movement into the cell (L-type Ca channels) –> triggers release of Ca from the sarcoplasmic reticulum (SR) via Ca-sensitive release channels, RyR2 –> increase in cytoplasmic Ca ++ –> binds to troponin C –> troponin I moves away from actin –> actin binds to myosin (ATP dependend process)

Question 23

How are low cytoplasmic calcium concentrations restored after contraction in cardiomyocytes?

Answer 23

80% of cytoplamic Ca increase comes from sarcoplasmic reticulum and

moves back and is sequestered into the SR via the SERCA (sarco/ednoplasmic reticulum Ca2+-ATPase) and Ca-binding storage proteins (most abundant” calsequestrin)

20% moves back out of the cells via the Na+-Ca2+ exchanger or Ca2+-ATPase pumps

Question 24

Explain the difference between isometric and isotonic muscle contractions

Answer 24

isometric muscle contraction - tension build up without actual shortening of the muscle “fixed length”
isotonic muscle contraction - shortening of the muscle without tension “fixed tension”

during systole - isometric contraction is the force needed to overcome afterload, isotonic contraction is then the actual shortening and forward movement of blood volume

Question 25

How does sympathetic tone increase cardiac contractility?

Answer 25

norepinephrine --> beta-1-adrenergic receptors --> activation of the **G-protein-cAMP-protein kinase A --> phosphorylates the Ca2+-channels** --> increases Ca permeability --> more Ca in the cell --> more muscle contraction can be achieved doesn't just increase IC Ca during that one beat but increases IC Ca++ stores --> more Ca++ during subsequent contractions more Ca++ --> more actin-myosin crossbinding

Question 26

Explain how norepinephrine exerts postive lusitropic effects

Answer 26

positive lusitropic effect = increaed diastolic time * noreponephrine --> phosphorylation of phospholamban on the SR Ca++-ATPase pump --> enhances rate of Ca++ retrapping * more IC Ca++ cc --> K channel permeability increases --> terminates the plateau phase of the action potential faster net effect: early repolarization

Question 27

Explain the *staircase phenomenon*

Answer 27

with increased HR --> more Ca moves into the cell per minute --> more IC Ca++ buildup --> more contractility

Question 28

Explain the Law of Laplace pertaining to wall tension and how this effects the work of contraction of cardiac myocytes during systole

Answer 28

tension = pressure x radius the pressure needed to overcome the tension is greater at a larger radius (i.e., early systole) and less at a small radius (i.e., late systole)

Question 29

How is the action potential conduction slowed as it passes through the AV node?

Answer 29

* small size AV nodal cells * slow rate of rise of the AV nodal cell action potentials

Question 30

What makes the electrical conduction in the Purkinje fibers so rapid. Why is this important?

Answer 30

* very large cell diameter * important, to facilitate coordinated contraction of the ventricular myocytes