Electron-conformational model of ryanodine receptor lattice dynamics.
We propose a simple, physically reasonable electron-conformational model for the ryanodine receptor (RyR) and, on that basis, present a theory to describe RyR lattice responses to L-type channel triggering as an induced non-equilibrium phase transition. Each RyR is modelled with a single open and a single closed (electronic) state only, described utilizing a s=12 pseudospin approach. In addition to the fast electronic degree of freedom, the RyR channel is characterized by a slow classical conformational coordinate, Q, which specifies the RyR channel calcium conductance and provides a multimodal continuum of possible RyR states. The cooperativity in the RyR lattice is assumed to be determined by inter-channel conformational coupling. Given a threshold sarcoplasmic reticulum (SR) calcium load, the RyR lattice fires due to a nucleation process with a step-by-step domino-like opening of a fraction of lattice channels, providing for a sufficient release to generate calcium sparks. The optimal mode of RyR lattice functioning during calcium-induced calcium release implies a fractional release with a robust termination due to a decrease in SR calcium load, accompanied by a respective change in effective conformational strain of the lattice. SR calcium overload is shown to result in excitation of RyR lattice auto-oscillations with spontaneous RyR channel opening and closure.
Moskvin
A S
AS
Ural State University, Ekaterinburg, Russia. alexandr.moskvin@usu.ru
Philipiev
M P
MP
Solovyova
O E
OE
Kohl
P
P
Markhasin
V S
VS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D015640:Ion Channel Gating; D008956:Models, Chemical; D011487:Protein Conformation; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium