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Biophysical Journal 87:243-255 (2004)
© 2004 The Biophysical Society

Effects of Ryanoids on Spontaneous and Depolarization-Evoked Calcium Release Events in Frog Muscle

Chiu Shuen Hui *, Henry R. Besch, Jr. {dagger} and Keshore R. Bidasee {ddagger}

* Department of Cellular and Integrative Physiology and {dagger} Department of Pharmacology and Toxicology, Indiana University Medical Center, Indianapolis, Indiana 46202; and {ddagger} Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198

Correspondence: Address reprint requests to Dr. Chiu Shuen Hui, Dept. of Cellular and Integrative Physiology, Indiana University Medical Center, 635 Barnhill Dr., Indianapolis, IN 46202. Tel.: 317-274-8238; Fax: 317-274-3318; E-mail: cshui{at}iupui.edu.

The effects of ryanoids on calcium sparks and transients were studied in voltage-clamped cut frog muscle fibers with a laser scanning confocal microscope. For each ryanoid employed, several sequential effects were observed, including: a), transient increases in spontaneous spark frequency; b), conversions of sparks to long-lasting steady glows; and c), occasional interruptions of the glows. The ratio of the amplitude of the glow induced by a ryanoid to that of the precursory spark followed the order: ryanodol > ryanodine > C10-Oeq-glycyl-ryanodine > C10-Oeq-ß-alanyl-ryanodol. This sequence of glow amplitudes parallels that of the subconductances induced by these ryanoids in single-channel studies, suggesting that the glows reflect Ca2+ fluxes through semiopen calcium release channels. Ryanoids also abolished depolarization-evoked sparks elicited with small pulses, and transformed the calcium release during depolarization to a uniform nonsparking fluorescence signal. The ratio of this signal, averaged spatially, to that of the control followed the order: ryanodol < ryanodine < C10-Oeq-glycyl-ryanodine < C10-Oeq-ß-alanyl-ryanodol, implying an inverse relationship with the amplitudes of ryanoid-induced glows. The observation that depolarization-evoked calcium release can occur after ryanoid suppression of calcium sparks suggests the possibility of a new strategic approach for treating skeletal muscle diseases resulting from leaky calcium release channels.




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[Abstract] [Full Text] [PDF]


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