Article,

Regulation of cardiac muscle Ca$^2+$ release channel by sarcoplasmic reticulum lumenal Ca$^2+$.

, and .
Biophys. J., 75 (5): 2302--2312 (November 1998)

Abstract

The cardiac muscle sarcoplasmic reticulum Ca$^2+$ release channel (ryanodine receptor) is a ligand-gated channel that is activated by micromolar cytoplasmic Ca$^2+$ concentrations and inactivated by millimolar cytoplasmic Ca$^2+$ concentrations. The effects of sarcoplasmic reticulum lumenal Ca$^2+$ on the purified release channel were examined in single channel measurements using the planar lipid bilayer method. In the presence of caffeine and nanomolar cytosolic Ca$^2+$ concentrations, lumenal-to-cytosolic Ca$^2+$ fluxes >/=0.25 pA activated the channel. At the maximally activating cytosolic Ca$^2+$ concentration of 4 microM, lumenal Ca$^2+$ fluxes of 8 pA and greater caused a decline in channel activity. Lumenal Ca$^2+$ fluxes primarily increased channel activity by increasing the duration of mean open times. Addition of the fast Ca$^2+$-complexing buffer 1,2-bis(2-aminophenoxy)ethanetetraacetic acid (BAPTA) to the cytosolic side of the bilayer increased lumenal Ca$^2+$-activated channel activities, suggesting that it lowered Ca$^2+$ concentrations at cytosolic Ca$^2+$-inactivating sites. Regulation of channel activities by lumenal Ca$^2+$ could be also observed in the absence of caffeine and in the presence of 5 mM MgATP. These results suggest that lumenal Ca$^2+$ can regulate cardiac Ca$^2+$ release channel activity by passing through the open channel and binding to the channel's cytosolic Ca$^2+$ activation and inactivation sites.

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