Lecture 2 - Extra reading Flashcards
Concentrations of Calcium in systole / diastole
high systole / low diastole
DA Eisner,2017
Control of intracellular Calcium cycling
1. Structural coupling
the transporters are organized within the dyad, linking the transverse tubule and
sarcoplasmic reticulum and ensuring close proximity of Ca entry to sites of release
DA Eisner, 2017
Control of intracellular calcium
2.Functional coupling
where the
fluxes across all membranes must be balanced such that, in the steady state, Ca influx equals Ca efflux on every beat
DA Eisner, 2017
What does Ca2+ do in membrane depolarisation
Ca2+ enters the cytosol primarily through a voltage-gated L-type Ca2+ current (ICa), which triggers Ca2+ release from the SR via Ca2+ release channels (ryanodine receptor 2, RyR2).
DH korzick, 2003
What are Ca2+ sparks?
Ca2+ sparks are currently thought to be the fundamental units of SR Ca2+ release occurring both at rest and during contractile activation
DH Korzick 2003
What is RyR2?
Ca2+ release channel in cardiac muscle
DH Korzick 2003
What can myocyte mishandling of Ca2+ lead to
central cause of both contractile dysfunction and arrhythmias
Bers DM 2002
What does myofilament sensitivity affect?
strength of contraction
Bers DM 2002
How is myofilament sensitivity affected?
reduced by acidosis /B-adrenergic activation
Enhanced by Mg2+/phosphate/caffeine/ionotropic drugs
Bers DM 2002
How does the Ca2+ load in the sacroplasmic reticulum affect Ca2+ release
High Ca2+ load directly increases the Ca2+ available for release
Bers DM 2002
what is the currently thought of the model for Ca2+ release and termination
controversial
currently CICR mediated by L-type calcium channels.
Bers DM 2002
what is required for therapeutic uses for the role of Ca2+ in EC coupling
distinguish between Ca2+ involved in excitation–contraction coupling and transcriptional regulation
Bers DM 2002
What does EC coupling depend on?
We now know that excitation–contraction coupling depends on a macromolecular protein complex or ‘calcium release unit’. The complex extends the extracellular space within the transverse tubule invaginations of the surface membrane, across the transverse tubule membrane into the cytoplasm and then across the sarcoplasmic reticulum membrane and into the lumen of the sarcoplasmic reticulum
Dulhunty AF, 2006
EC coupling hypothesis or reality?
all evidence strongly supports the mechanical coupling mechanism for EC coupling, mechanical coupling remains a hypothesis. The ultimate experiment will be visualization of the conformational changes that occur in the DHPR and the RyR during EC coupling
Dulhunty AF, 2006
