Why are we interested in lumenal regulation of RyR2?

Ryanodine Receptors from cardiac muscle open in response to a small depolariztion-induced entry of Ca2+ ("trigger Ca2+"). Thus, the RyR it is a calcium-sensitive channel. Its opening allows a massive release of Ca2+ stored inside the sarcoplasmic reticulum. Released Ca2+ induces further opening of RyR initiating an intrinsically positive feedback that allows the rapid increase of intracellular Ca2+ concentration and muscle contraction. A molecular mechanism must exist to counter the intrinsic tendency of RyRs to remain open. One of the current hypotheses is that RyR2 close in response to the reduction of Ca2+ in the lumen of the sarcoplasmic reticulum. The sensor for this decrease in Ca2+ would be the intrareticular protein calsequestrin. David Baéz, an undergraduate student of Biochemstry from the Catholic University of Valparaíso is experimentally testing this ideas in his thesis work. Watch David working in the lab: http://ryanodine.camarades.com/