3-1: 8/25: Excitation-Contraction Coupling

Front 1

What are terminal cisternae?

Back 1

Regions where T-tubules abut SR at right angles; allows for efficient link of membrane excitation, Ca2+ influx and intracellular Ca2+ release

Front 2

Function of Ryanodine Receptor

Back 2

Four RyR2 monomers form fnal Ca2+ releasing channel in SR membrane

Front 3

SERCA (SR Ca2+-ATPase): Role

Back 3

SERCA: pump that brings ATP back into cell

Front 4

PL (Phospholamban): Role

Back 4

INhibitory and blocks SRCA

When PL becomes Pi'd, SRCA is relieved and uninhibited

Front 5

What is the effect of increased PL phosphorylation on contraction?

Back 5

Would increase number of contractions with reuptake is fastened, and next contraction can ensure sooner

Front 6

What is E-C coupling gain?

What are potential causes for a
decrease in E-C coupling gain as seen in heart failure?

Back 6

E-C coupling gain: efficiency of Incoming Ca2+ at triggering Ca2+ from SR

Potential Causes:
Ryanidine would lead to opening of channel

-Functional defects in L-type Ca2+ channel (next to Ryanidine channel)
-Increased space between LTCC (T tubule) and RyR2 (Ryanadine Receptor)
-Abnormalities in RyR2
-Decrease in SR Ca2+ content due to:
-Reduced re-uptake of Ca2+ into SR
-Increased Ca2+ extrusion from cell
-Ca2+ leak from SR during diastole

Front 7

Mutations in __________ is associated with familial cardiomyopathy.

What is a cardiomyopathy?

Back 7

Myutations in MYOFILAMENT PROTEINS are assocd w/familial (genetic forms) cardiomyopathy

Cardiomyopathies are a group of heart disorders in which major structural abnormality is limited to myocardium (can be hypertrophic, dilated, and restrictive).

Front 8

Isometric contraction occurs at constant ________.

Back 8

Length (muscle cannot shorten, but it can develop tension)

Front 9

Active Tension vs Resting Tension

What is total tension?

Back 9

Active Tension: Tension dev'd upon stimulation when length is held constant. Depends on muscle length at which contraction occurs.

Resting Tension: force required to stretch a resting muscle to different length (optimal overlap of thin and thick filaments)

Total Tension = Sum of resting tension plus active tension.

Front 10

Isotonic contraction occurs at constant _________.

Back 10

Constant Force

One end of muscle is free, and the muscle is compelled to lift a weight

(Weight attached to muscle provides afterload)

Front 11

Preload vs Afterload

Back 11

Time during contraction when a muscle first interacts with load is used to distinguish:

Preload (weight stretches a muscle before it contracts; muscle doesn't 'see' afterload)--chamber filling

Afterload (not evident to the muscle during the resting state; encountered when it begins to contract)--when heart needs to overcome additional load

Front 12

Targets of PKA (protein kinase A) and its effects

Back 12

PKA adds Pi's to following targets:
LCC (more Ca2+ inflx)
Ryanidine Receptor (more SR Ca2+ release)
PL (or PLB--phospholambin): More SR Ca2+ UPTAKE
Troponin I: facilitates binding of myosin to actin

Front 13

Significance of Ryanodine Receptor N Terminal

Back 13

Has space to pind kinases and phosphotases (Kinase A is associated to N terminus)

Also has FKBP: stabilizes Ryanodine Receptor

Front 14

Function of FKBP, Location

Back 14

Stabilizes Ryanodine Receptor; located on Ryanodine N terminus

Front 15

Phosphodiesterase Inhibitors: Role

Back 15

Rise of cAMP can be due to inhibition of phosphodiesterase, which leads to increase in Ca2+ cycling and contraction

Front 16

What effect does heart failure have on catecholamine levels?

What effect does this have on PKA events in the heart?

List three classes of drugs used to treat this condition in acute and chronic settings.

Back 16

More epi, more NE-->receptor downregulation, thus dec in cAMP

Thus phosphorylation events are decreased

beta-adrenergic agonists (acute situations)
beta-adrenergic blockers (low doses in chronically ill patients, protects receptors from constant drive of catecholamines)
phosphodiesterase inhibitors

Front 17

What experimental therapies are used to treat altered contractility regulation in heart failure?

Back 17

Stabilize Ryanodine Receptor

Increase PLB-Phosphorylation; Decrease PLB expression

Increase SERCA expression

Front 18

L-Type Ca2+ Channel Blockers: Consequences

Back 18

Reduction of influx of Ca2+

Front 19

What is the mechanism and effect of Cardiac Glycosides?

Back 19

Inhibit Na+/K+ ATPase

Destroy Na+/K+ gradient, more Na+ inside cell, thus Na+/Ca2+ exchanger drives less Ca2+ out of cell
Ex; DIGITALIS

Results in increased intracell Ca2+ in SR, more Ca2+ to myofils, and INCREASED CONTRACTION (positive ionotropic effect)