Regulation of cardiac muscle Ca$^2+$ release channel by sarcoplasmic
reticulum lumenal Ca$^2+$.
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.
Description
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Links and resources
- URL:
- http://www.biophysj.org/cgi/content/full/75/5/2302
- BibTeX key:
- Xu_1998_2302
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