EC Coupling I & II Flashcards
T-tubules are ____________.
transverse tubules, invaginations of the cellular membrane that convey action potentials to spots within the cell
What is a calsequestrin?
A protein that binds calcium with low affinity and high capacity that helps store calcium within smooth endoplasmic reticulum
What phase inactivates DHPRs?
Phase 3
What are SERCA and where are they located?
Smooth endoplasmic reticulum calcium ATPases; they are on the longitudinal SER and pump 2 calcium ions into the SER for every ATP molecule hydrolyzed
Calsequestrin is located in the ______ of the smooth endoplasmic reticulum.
terminal cisternae
What do ryanodine receptors do?
They release calcium into the cytosol in response to extracellular calcium.
Unlike skeletal muscle, cardiac muscle __________ extracellular calcium.
requires the entry of
Cardiac myocytes do not have _________, found in skeletal myocytes.
the plunger-style calcium pumps which, upon depolarization of the cell membrane, pull open the RyR1 receptors of the SER membrane
How does calcium exit the cytoplasm?
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
Heart failure is a generic term for ____________.
insufficient cardiac output
Explain how digitalis works.
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].
Norepinephrine is released by _________ and does three things to the heart: ___________.
sympathetic nerve terminals; (1) increases heart rate, (2) increases contractility, and (3) increases relaxation rate
How does norepinephrine achieve its effect?
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)
Phospholambin normally ___________, but phosphorylating it _________.
inhibits SERCA; causes it to dissociate, thereby increasing speed of relaxation
Timothy syndrome presents with _______ and results from ________.
arrhythmias, cognitive dysfunction, and immune problems; defects in Cav1.2 that result in channels that take a longer time to turn off
Those with Brugada syndrome have defects in __________.
either Nav or CaL channels that results in shortened QT interval
What is CPVT?
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
The cardiac isoform of calsequestrin is __________.
calsequestrin 2
Why would defective RyR2 channels or defective calsequestrin cause arrhythmia?
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.
What do cardiologists give CPVT patients?
ß-blockers, which raise the threshold for action potentials and decrease the likelihood of aberrant action potentials
CaL channels are inactivated by __________.
high levels of calcium in the SR
