Effects of ryanoids on spontaneous and depolarization-evoked calcium release events in frog muscle.
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)-beta-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)-beta-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.
Hui
Chiu Shuen
CS
Department of Cellular and Integrative Physiology, Indiana University Medical Center, Indianapolis, 46202, USA. cshui@iupui.edu
Besch
Henry R
HR
Bidasee
Keshore R
KR
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D008333:Mandelic Acids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D011896:Rana temporaria / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology*
D000470:Alkaloids; D008333:Mandelic Acids; D012433:Ryanodine; C005419:oxybutynin; D002118:Calcium