Heart 6 Flashcards
Function of the sarcolemma
Propagation of action potentials; controls calcium influx into the cell via activation of slow inward calcium current
Function of the transverse tubules
Transmit electrical activity to the cell interior; located at Z-lines
Function of the sarcoplasmic reticulum
Intracellular calcium storage site
Function of the terminal cisternae
Site where calcium influx triggers opening of calcium release channels to initiate contraction
Longitudinal cisternae
Possible site of calcium reuptake to initiate relaxation
Function of troponin C
Calcium receptor on contractile protein
What is the difference in the contractile mechanism between cardiac and skeletal muscle?
There is none; they are the same
What is the immediate result of depolarization of T-tubules?
Activates calcium influx via slow inward calcium current
When slow inward calcium current flux is in effect, where does the calcium bind and what does it do?
Binds to the calcium release channels on the sarcoplasmic reticulum and opens them
What is the name for the SR calcium release channels?
Ryanodine reeptors
What initiates contraction of the heart muscle?
Calcium that is released fro the sarcoplasmic reticulum binds to troponin C
How long is contraction maintained?
As long as cytosolic calcium remains elevated
How is relaxation initiated?
Removal of cytosolic calcium by
- sarcoplasmic calcium uptake
- calcium efflux out via NCX
- calcium efflux out via sarcolemmal calcium pump
Difference in length between cardiac and skeletal cells
Cardiac are small (50-100 um); skeletal cells could run the whole length of the muscle
Difference in connectivity of cells between cardiac and skeletal
Cardiac cells have a syncytium that connects all the cells via gap junctions. Skeletal muscle cells are all individual
Difference in activation between cardiac and skeletal cells
Cardiac: activated by cell-to-cell conduction
Muscle: activated by neurochemical transmission at neuromuscular junctions
Calcium dependence during contraction: cardiac vs skeletal
Cardiac: contraction is dependent on calcium influx (CICR)
Skeletal: Contraction is mediated by voltage sensors
Cardiac vs skeletal: how is contraction amplitude regulated?
Cardiac: via slow calcium current and sarcoplasmic calcium content
Skeletal: by frequency of action potentials and central recruitment of muscle fibers
Cardiac vs skeletal: summation
Cardiac: no summation or tetanus
Skeletal: summation and tetanus generates maximum tension
Anaerobic or aerobic: cardiac vs skeletal
Cardiac: highly aerobic, 35% mitochondrial density
Skeletal: highly anaerobic, 2% mitochondrial density
Are catecholamines positive or negative inotropic agents?
Positive
Mechanism of catecholamines
- Binds to beta-adrenergic receptors
- Gs activates adenylate cyclase to increase cAMP
- cAMP activates cAMP-dependent protein kinase A
- PKA phosphorylates stuff
What does PKA phosphorylate?
- Calcium channels to increase influx
- Phospholamban to increase SR calcium uptake
- Both #1 and #2 increase CICR
Effectively, what are the effects of PKA phosphorylation?
Phospholamban phosphorylation enhances efficacy of relaxation while shortening time it takes to do so.
Increasing CICR increases contraction strength
What is an example of a cardiac glycoside?
Digitalis
Are cardiac glycosides positive or negative inotropic agents?
Positive
For what pathology are cardiac glycosides prescribed?
Congestive heart failure
Mechanism of cardiac glycosides
- Inhibits Na-K pump
- Increased intracellular [Na] decreases the [Na] gradient
- Calcium extrusion by NXC is reduced, increasing intracellular [Ca]
- Increased SR [Ca] leads to greater calcium release, and therefore, contraction
Examples of calcium channel blockers
Verapamil, diltiazem, nifedipine
For what purpose are calcium channel blockers used clinically?
As vasodilators and anti-arrhythmic agents
Mechanism of calcium channel blockers
- Blocks calcium influx via calcium channels (i.e., blocks CICR)
- Decreased SR calcium release and SR calcium content leads to less contraction on vascular smooth muscle (vasodilation)
Where do the anti-arrhythmic effects of calcium originate?
inhibition of slow inward calcium current, which inhibits conduction of AV node action potential to block SVT
What is an unwanted side effect of calcium channel blockers?
Due to decrease in the CICR, it has negative inotropic effects on the heart
Force-frequency relationship
Beating rate and rhythm of the heart influences cardiac contraction amplitude by altering contractility. Changes in the cycle length alter the time available for intracellular calcium handling, which alters contractility
