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

• Published in: Biophysical journal 2004-07, Vol.87 (1), p.243-255
• Main Authors: Hui, Chiu Shuen, Besch, Henry R., Bidasee, Keshore R.
• Format: Article
• Language: English
• Subjects: Alkaloids - pharmacology; Animals; Anura; Calcium; Calcium - metabolism; Channels, Receptors, and Transporters; Electric Stimulation; Freshwater; Frogs; Mandelic Acids - pharmacology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Microscopy, Confocal; Molecular biology; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; Muscular system; Rana temporaria - physiology; Ryanodine - pharmacology
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.103.031435

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 > C 10-O eq-glycyl-ryanodine > C 10-O eq- β-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 Ca 2+ 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 < C 10-O eq-glycyl-ryanodine < C 10-O eq- β-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.