EC Coupling I & II

Question 1

T-tubules are ____________.

Answer 1

transverse tubules, invaginations of the cellular membrane that convey action potentials to spots within the cell

Question 2

What is a calsequestrin?

Answer 2

A protein that binds calcium with low affinity and high capacity that helps store calcium within smooth endoplasmic reticulum

Question 3

What phase inactivates DHPRs?

Answer 3

Phase 3

Question 4

What are SERCA and where are they located?

Answer 4

Smooth endoplasmic reticulum calcium ATPases; they are on the longitudinal SER and pump 2 calcium ions into the SER for every ATP molecule hydrolyzed

Question 5

Calsequestrin is located in the ______ of the smooth endoplasmic reticulum.

Answer 5

terminal cisternae

Question 6

What do ryanodine receptors do?

Answer 6

They release calcium into the cytosol in response to extracellular calcium.

Question 7

Unlike skeletal muscle, cardiac muscle __________ extracellular calcium.

Answer 7

requires the entry of

Question 8

Cardiac myocytes do not have _________, found in skeletal myocytes.

Answer 8

the plunger-style calcium pumps which, upon depolarization of the cell membrane, pull open the RyR1 receptors of the SER membrane

Question 9

How does calcium exit the cytoplasm?

Answer 9

Through SERCA and sodium-calcium exchangers (3 Na+ for 1 Ca2+); SERCA dominates, because there is no voltage gradient between the inside of the SER and the cytoplasm, whereas in the cytoplasm the calcium is pushed against its gradient

Question 10

Heart failure is a generic term for ____________.

Answer 10

insufficient cardiac output

Question 11

Explain how digitalis works.

Answer 11

Digitalis is an old treatment for heart failure. It inhibits the Na-K pump, thereby raising the level of intracellular sodium. One consequence of this is that the Na-Ca exchanger shifts to pump Na out and Ca in. Ca then gets shuffled to the SER and thus more Ca is present during the next heart beat. The heart contracts more vigorously with increased SER [Ca].

Question 12

Norepinephrine is released by _________ and does three things to the heart: ___________.

Answer 12

sympathetic nerve terminals; (1) increases heart rate, (2) increases contractility, and (3) increases relaxation rate

Question 13

How does norepinephrine achieve its effect?

Answer 13

Through ß-adrenergic receptors, it activates protein kinase A; PKA then phosphorylates the CaL channel (increasing its activity), RyR2 (increasing its activity), troponin (increasing its speed of releasing calcium and thus increasing lusitropy), and phosphorylating phospholambin (stopping its inhibition of SERCA and thus speeding lusitropy and increasing inotropy)

Question 14

Phospholambin normally ___________, but phosphorylating it _________.

Answer 14

inhibits SERCA; causes it to dissociate, thereby increasing speed of relaxation

Question 15

Timothy syndrome presents with _______ and results from ________.

Answer 15

arrhythmias, cognitive dysfunction, and immune problems; defects in Cav1.2 that result in channels that take a longer time to turn off

Question 16

Those with Brugada syndrome have defects in __________.

Answer 16

either Nav or CaL channels that results in shortened QT interval

Question 17

What is CPVT?

Answer 17

Catecholaminergic polymorphic ventricular tachycardia; it is a disorder from mutations in RyR2, similar to mutations that cause malignant hyperthermia, that cause RyR2 to be more sensitive to Ca or to constantly leak Ca; people with this disorder have normal ECGs until they exercise or receive catecholamine

Question 18

The cardiac isoform of calsequestrin is __________.

Answer 18

calsequestrin 2

Question 19

Why would defective RyR2 channels or defective calsequestrin cause arrhythmia?

Answer 19

Leakage of calcium into the cytosol prompts the sodium-calcium exchanger to pump calcium out; in doing so, it gradually depolarizes the membrane and can thus generate an ectopic action potential.

Question 20

What do cardiologists give CPVT patients?

Answer 20

ß-blockers, which raise the threshold for action potentials and decrease the likelihood of aberrant action potentials

Question 21

CaL channels are inactivated by __________.

Answer 21

high levels of calcium in the SR