Present address: Department of Neurology, Higashi Nagoya Hospital, 101 Umemorizaka 5-chome, Meito-ku, Nagoya, Aichi 466-0065, Japan.
Calcium dependence of the priming, activation and inactivation of ryanodine receptors in frog motor nerve terminals
Article first published online: 26 AUG 2010
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 32, Issue 6, pages 948–962, September 2010
How to Cite
Soga-Sakakibara, S., Kubota, M., Suzuki, S., Akita, T., Narita, K. and Kuba, K. (2010), Calcium dependence of the priming, activation and inactivation of ryanodine receptors in frog motor nerve terminals. European Journal of Neuroscience, 32: 948–962. doi: 10.1111/j.1460-9568.2010.07381.x
- Issue published online: 17 SEP 2010
- Article first published online: 26 AUG 2010
- Received 1 May 2010, revised 12 June 2010, accepted 21 June 2010
- Ca2+ channel and Ca2+ nanodomain;
- Ca2+ release;
- Ca2+-induced Ca2+ release;
- endoplasmic reticulum
We studied the effects of varying extracellular Ca2+ ([Ca2+]o) and Ca2+ channel density and intracellular loading of Ca2+ chelators on stimulation-induced rises in intracellular Ca2+ ([Ca2+]i) in frog motor nerve terminals with Ca2+ imaging. The slowly waxing and waning components of rises in [Ca2+]i induced by repetitive tetani were suppressed by blockers of Ca2+ pumps of the endoplasmic reticulum (thapsigargin and cyclopiazonic acid) and a blocker of ryanodine receptors [8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride] without affecting the initial quickly-rising component, thus reflecting the priming (and then subsequent rapid activation) and inactivation phases of Ca2+-induced Ca2+ release (CICR) from the endoplasmic reticulum. A short tetanus-induced rise in [Ca2+]i was proportional to [Ca2+]o, whereas the component of CICR was non-linearly related to [Ca2+]o with saturation at 0.9 mm. The progressive blockade of Ca2+ channels by ω-conotoxin GVIA caused proportional decreases in CICR and short tetanus-induced [Ca2+]i rises. Intracellular loading of BAPTA and EGTA reduced the magnitude of CICR as well as short tetanus-induced rises in [Ca2+]i with a greater effect of BAPTA than EGTA on CICR. The time to peak and the half decay time of CICR were prolonged by a low [Ca2+]o or Ca2+ channel blocker or [Ca2+]i chelators. These results suggest that ryanodine receptors sense the high [Ca2+]i transient following single action potentials for triggering CICR, whereas the priming and inactivation processes of CICR sense a slower, persisting rise in [Ca2+]i during and after action potential trains. A model is presented that includes CICR activation in elementary units.