Chapter 3: Excitation Contraction (EC) Coupling: Calcium, the EC Powerhouse

Question 1

Cardiac myocyte

Answer 1

The functional unit of the pumping mechanism of the heart

Question 2

Components of cardiac myocyte

Answer 2

1. Sarcolemma (cell membrane)
2. Sarcomere (containing the components necessary to contract and relax the cell)
3. Mitochondria
4. Sarcoplasmic reticulum (SR)

Question 3

T -tubules

Answer 3

Deep invaginations of the sarcolemma

Question 4

Function of T-tubules

Answer 4

Allow intimate coupling of the sarcolemma (containing calcium channels) with the SR (containing intracellular stores f Ca2+)

Question 5

Separation of individual cardiac cells + function

Answer 5

Separated by intercalated disks (containing gap junctions) that allow for the passage of electrical activity

Question 6

Components of myofibrils in cardiac myocytes

Answer 6

• actin (main component of thin filament along with proteins troponin and tropomyosin)
• myosin (thick filament)

Question 7

Function of myosin

Answer 7

Pivoting head forms cross-bridges to actin filaments

Question 8

Cross bridge cycling

Answer 8

• ATP fueled

- formation and breakage of cross-bridges

Question 9

Caciums role in contraction-relaxation cycle

Answer 9

1. Calcium binds to troponin which results in exposure of myosin binding sites and initiates and maintains cross-bridge cycling that leads to contraction
2. In absence of calcium (between contractions when Ca2+ is pumped out) troponin and tropomyosin bind to actin ensuring relaxation

Question 10

Two mechanisms of calcium entry into the cell

Answer 10

1) The sodium-calcium exchanger (moves 3 Na+ out of the cell for every 1 Ca2+ into the cell during systole)
2) Voltage gated L–type Ca2+ in cell membrane

Question 11

Dyad

Answer 11

Microdomain consisting of SR and adjacent T tubule

Where Ca2+ induced Ca2+ release occurs

Question 12

Calcium-induced calcium release

Answer 12

After the movement of Ca2+ across the sarcolemma (by 2 mechanisms) the concentration of Ca2+ in the microdomain/dyad rises to point where it is sufficient to open the Ca2+ release channels in the SR

Question 13

Relaxation steps

Answer 13

1. Ca2+ transport back into SR by SR Ca2+ pump
   - once inside bound to calsequestrin
   - held in terminal pockets (cisternae) of the SR so readily available for next AP
2. Ca2+ moved back across he sarcolemma by:
   i) Ca2+ pump
   ii) Na+/Ca2+ exchanger

Question 14

Action of the SNS on the heart

Answer 14

release norepinephrine
-interacts with adrenergic receptors on cell membrane of myocytes
Causes:
1) Inotropy
2) Chronotropy
3) Lusitropy

Question 15

Inotropy

Answer 15

Contractility or the ability of the heart to develop force at a given muscle fiber length (assuming hr is constant and volume of ventricles at end of diastole is constant)

Question 16

Chronotropy

Answer 16

Increase in speed of cardiac contraction

Question 17

Lusitropy

Answer 17

Acceleration of cardiac relaxation

Question 18

Chronotropy cause

Answer 18

• norepinephrine and epinephrinne are released from SNS
• act on B1-receptor on cardiac pacemaker cells (SA node)
• B-adrenergic stimulation changes the ionic properties within the cells so they spontaneously initiate APs faster (increasing heart rate)

Question 19

Parasympathetic effect on chronotopy

Answer 19

Acetylcholine binds to muscarinic receptors and reduced the spontaneous rate at whih APs are generated in the SA node

Question 20

Positive inotrope

Answer 20

Change in inotropy due to administration of a drug

Question 21

MOA of positive inotropes

Answer 21

1) many activate B-adrenergic receptors
2) activates series of secondary messengers within the cardiac myocytes
3) Protein kinase A -induced phosphorylation of specific membrane proteins –> incuding phospholamban and L-type Ca2+ channels
4) Phosphorylated phospholamban acts on SR (a SE membrane protein) -facilitates reuptake of Ca2+ by SR
5) Increase in the amount of ca2+ available for cross-bridge cycling
6) more forceful contraction

Question 22

Lusitropy MOA

Answer 22

• the result of activation of phospholamban
• this enhances Ca2+ reuptake into the SR after contraction
• thereby facilitating its removal from the contractile filaments and preparing for next contraction