Excitation-Contraction Coupling Flashcards by Rachel Schultz

How is contraction strength regulated in myocytes

Individual myocytes change contraction strength

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What factors can regulate cardiac contraction

Length dependent
- frank starling relationship (F/SV vs EDV)
- length tension relationship
Length independent
- changes in contractility that are not related to sarcomere length

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How does the frank-starling graph change when increased contractility? what possible inotropes can cause this?

SV vs EDV: Shift left and up (causes smaller EDV)
Positive inotropes: noradrenaline, adrenaline, cocaine, amphetamines, digitalis (digoxin)

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How does the frank-starling graph change when decreased contractility? what possible inotropes can cause this?

SV vs EDV: shift right and down (less blood pushed out, larger EDV)
Negative inotropes: propranolol, nifedipine, ACh

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What are inotropes?

Inotropes are drugs that tell your heart muscles to beat or contract with more power or less power

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How does sympathetic and parasympathetic stimulation effect contractility? State shifts of Frank-starling curve.

Sympathetic- increases contractility. Shift up and left.
Parasympathetic- decreases contractility. Shift down and right.

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Define inotropy

Force of contraction

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Define chronotropy

Rate of heart beating

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Dromotropy

Rhythmicity ofcontraction

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Where does excitation-contraction coupling begin

T tubules

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What ways can myocytes use to vary contraction

Change length of AP
Amount of Ca2+ let into the cell from Cav1.2 channel OR sarcoplasmic reticulum (SR)

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What is the name of the calcium channel in sarcolemma

Cav1.2

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What releases Ca from the SR

Ryanodine receptor RyR2

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How is calcium released from SR

Calcium enters cell through Cav1.2 channels in sarcolemma. This calcium binds to ryanodine receptors of SR and allows RyR2 to open releasing calcium. Mechanism- Ca induced, Ca release (CICR)

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Name the L-type Ca channel, when does it open

Cav1.2
Opens at -35mV
Alpha1c subunit

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Name the two calcium sources used in excitation-contraction coupling and state their contribution percents

Cav1.2- 10-40%
RyR2- 60-90%

Is Ca moving up or down its concentration gradient when going through: Cav1.2 or NCX channels

Cav1.2- down gradient (into cell)
NCX- up gradient (out of cell)

What does NCX channel exchange? How can it function like this?

3 Na into cell, 1 Ca out of cell (net +1 in)
Energy generated by Na in, is used to get Ca out

How does SERCA-2A work? What does it pump?

2 Ca enter SR with the help of ATP (active transport)

What is the role of PLB?

PLB- phospholamban inhibits ATP activity
For excitation- contraction coupling- it inhibits ATP used in SERCA-2A therefore no Ca re-absorbed into SR

Name all the channels in the sarcolemma

Cav1.2
NCX
Sodium-potassium pump (3 Na out, 2 K in)

How is cAMP used in myocytes vs sinoatrial node?

Myocytes: cAMP binds to protein kinase A (PKA) which phosphorylates phospholamban (PLB), Cav1.2, TnI

SAN: cAMP activates HCN channels

What phosphorylates PLB and how does this effect PLB

PLB- phospholamban
PKA phosphorylates PLB
Causes PLB to detach from SERCA-2A- allowing more Ca reuptake

What happens to force of contraction if SERCA activity is increased? How?

PKA increases SERCA activity
Force of contraction is increased
- faster relaxation
- more SR Ca release (b/c more uptake with PLB removed- so more load in SR)
- larger depolarization phase

What three components of excitation-contraction coupling are increased by PKA activity? How do these components affect the force of contraction?

SERCA-2A activity CA2+ entry via Cav1.2 channels Relaxation rate *all increase force of contraction*

How does PKA affect Cav1.2 channels? What does this mean for the cell in general?

Phosphorylates channel, increases open probability. This increases Ca current into cell and calcium-induced calcium release (CICR) In general- increases force of contraction

What is the outcome of PKA phosphorylating TnI

TnI directly bound to actin and TnC. Phosphorylation causes a decreased affinity of TnC site II for Ca2+ (site II-initiate contraction). This promotes faster relaxation rate. Overall force of contraction increases- Ca stripped faster therefore can be reused faster

What is the sympathetic regulation pathway related to excitation-contraction coupling in myocytes

Noradrenaline binds to beta1 adrenergic receptor- Gs subunit leaves to activate adenylyl cyclase- creates cAMP- activates PKA- which then phosphorylates many things (PLB, Cav1.2, TnI, RyR) *RyR- increase fractional Ca release from SR*

Parasympathetic stimulation effect on excitation-contraction coupling

Decrease contractility, inhibit cAMP production therefore PKA can not be activated

Pharmacological regulation of excitation-contraction coupling *in full*

Sympathomimetics - stimulate sympathetic NS • cocaine - blocks NA re-uptake by neurons • amphetamines - release NA from storage vesicles • positive inotrope Sympatholytics - inhibit the sympathetic NS • β blockers (e.g. propranolol) • negative inotrope Digitalis (Digoxin) • a positive inotrope • inhibits Na/K-ATPase

Pharmacological regulation of E-C coupling: what things stimulate sympathetic nervous system, provide examples

Sympathomimetics Ex. Cocaine, amphetamines, positive inotropes

Pharmacological regulation of E-C coupling: what things inhibit sympathetic nervous system, provide examples

Sympatholytics Ex. Beta blockers (propranolol), negative inotropes

What does cocaine do

Blocks noradrenaline re-uptake by neurons

What do amphetamines do

Release noradrenaline from storage vesicles

What does digitalis (digoxin) do and what problems does this cause E-C coupling

Inhibits Na/K ATPase (3Na out, 2K in). When no pump, the NCX channel works in the opposite direction Na out of cell and down gradient (b/c now high concentration inside). Ca into cell and down gradient. *normal NCX- 3Na into cell and down gradient, 2Ca out of cell and up gradient* Overall this will increase the resting membrane potential!

Which pharmacological regulation increase the resting membrane potential? how?

Digitalis (digoxin) Inhibit Na/K ATPase. High Na concentration inside cell and reduction in K in cell increases resting membrane potential