excitation- contraction coupling

Question 1

explain the process of Ca induced Ca release

Answer 1

• ca influx through L-type channels during plateau phase of AP
• contraction + relaxation occurs within this phase
• Ca signal amplified via the binding of Ca to RyR channels located within the membrane of the SR
• L-type channel is directly opposite the RyR, physical interaction between the 2 channels stimulates activation and opening of RyR.
• localised ca sparks

Question 2

Where are these L-type channels found?

Answer 2

• deep invaginations within the myocyte
• essential for E-C coupling
• located within T-tubules
• close association with RyR (foot projections)

Question 3

list the mechanisms for removing ca from the myocyte .

Answer 3

• Na/Ca exchanger (NCX1)
• PMCA- Ca (ATPase)
  (minor)

major mechanisms include

• SERCA2a
• PLN inhibits SERCA at rest
• phosphorylation of PLN increases ca uptake by SERCA
• most important mechanism
• sequestration into the mt via highly selective Ca channels

Question 4

contraction and relaxation occur during what phase?

Answer 4

• plateau
• when the cell is refractory (na channels inactivated)
• ensures no AP is fired during the relaxation process so filling of the ventricles is not compromised

Question 5

how can we increase isotropy/contractility of the heart?

Answer 5

• increasing available intracellular ca
• increased opening of L-type channels (adrenergic agonists)~
• increased opening of RyR
  (mediated via cAMP pathway ``B1r)
• inhibition of NXC1 (cardiac glycosides)
• inhibiting PMCA

Question 6

how can the force of contraction be increased by starlings law of the heart?

Answer 6

• increased ventricular filling by increasing EDV
• increased stretching of the myocytes
• increases sarcomere length leading to increased ca sensitivity of the myofilament
• length dependent increase in ca sensitivity
• filaments closer together increasing likelihood of forming C-Bs
• stretch mediated Ca channels open increasing ca influx enhancing CICR
• all increase the force of contraction (no. of CBs formed)

Question 7

why is relaxation of the heart important?

Answer 7

• diastole
• removal of intracellular calcium
• sequestration important for increasing ca reserves in the SR / mt
• no other AP can be generated during the RP
• allows sufficient filling during diastole

Question 8

What is the role of catecholamines at B1-r??

Answer 8

• P of PLN (usually inhibits SERCA)
• removal of inhibition of SERCA2a allows for increased sequestration into the SR
• P of TN-I leading to increased rate of removal of ca from TN-C (all mediated via cAMP)
• increases rate of relaxation - lusitropy - just as important as contraction is. (allows faster relaxation)
• increased S allows for increased Ca stores and effectively an even greater release of Ca during the next systole

Question 9

how can we increase SV?

Answer 9

• starlings law of the heart (length dependent increase in Ca sensitivity of myofilaments)
• increased contractility / inotropy (Nad)

Question 10

What is the effect of HR on the force of contraction?

Answer 10

• Hr increases and so does the force of contraction
• staircase phenomenon / Bowditch effect
• increased HR increases SR ca content

Question 11

Explain the Bowditch effect

Answer 11

• during an increased HR there is a greater influx of Ca through L-T channels
• at positive Vm NCX1 works in reverse pumping Ca in and Na outwards
  (cell at +Vm during contraction phase)
• stimulation of SERCA leading to greater uptake of Ca from both of the above
• increased Ca concentration activate caM kinase 2, essentially activating PLN and removing inhibition of SERCA

( as when activated PLN relieves inhibition on SERCA)