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Pflugers Arch. 2010 Sep;460(4):767-76. doi: 10.1007/s00424-010-0839-8. Epub 2010 Apr 24.

Ryanodol action on calcium sparks in ventricular myocytes.

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1
Department of Molecular Biophysics & Physiology, Rush University Medical Center, Chicago, IL 60612, USA.

Abstract

The action of ryanodol on single cardiac ryanodine receptor (RyR2) channels in bilayers and local RyR2-mediated Ca(2+) release events (Ca(2+) sparks) in ventricular myocytes was defined. At the single-channel level, ryanodol intermittently modified single channels into a long-lived subconductance state with an average duration of 3.8 +/- 0.2 s. Unlike ryanodine, ryanodol did not change the open probability (Po) of unmodified channels, and high concentrations did not promote full-channel closure. Ryanodol action was Po dependent with the K (D) varying roughly from 20 to 80 muM as Po changed from approximately 0.2 to 1, respectively. Ryanodol preferentially bound during long channel openings. In intact and permeabilized rat myocytes, ryanodol evoked trains of sparks at active release sites resulting in a significant increase in overall spark frequency. Ryanodol did not increase the number of active release sites. Long-lived Ca(2+) release events were observed but infrequently, and ryanodol action was readily reversed upon drug washout. We propose that ryanodol modifies a few channels during a Ca(2+) spark. These modified channels mediate a sustained low-intensity Ca(2+) release that repeatedly triggers sparks at the same release site. We conclude that ryanodol is an easily generated reversible probe that can be effectively used to explore RyR2-mediated Ca(2+) release in cells.

PMID:
20419313
PMCID:
PMC3315696
DOI:
10.1007/s00424-010-0839-8
[Indexed for MEDLINE]
Free PMC Article
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