title: Calcium dependence of the priming, activation and inactivation of ryanodine receptors in frog motor nerve terminals.
abstract: We studied the effects of varying extracellular Ca(2+) ([Ca(2+) ](o) ) and Ca(2+) channel density and intracellular loading of Ca(2+) chelators on stimulation-induced rises in intracellular Ca(2+) ([Ca(2+) ](i) ) in frog motor nerve terminals with Ca(2+) imaging. The slowly waxing and waning components of rises in [Ca(2+) ](i) induced by repetitive tetani were suppressed by blockers of Ca(2+) 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 Ca(2+) -induced Ca(2+) release (CICR) from the endoplasmic reticulum. A short tetanus-induced rise in [Ca(2+) ](i) was proportional to [Ca(2+) ](o) , whereas the component of CICR was non-linearly related to [Ca(2+) ](o) with saturation at 0.9 mm. The progressive blockade of Ca(2+) channels by ω-conotoxin GVIA caused proportional decreases in CICR and short tetanus-induced [Ca(2+) ](i) rises. Intracellular loading of BAPTA and EGTA reduced the magnitude of CICR as well as short tetanus-induced rises in [Ca(2+) ](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 [Ca(2+) ](o) or Ca(2+) channel blocker or [Ca(2+) ](i) chelators. These results suggest that ryanodine receptors sense the high [Ca(2+) ](i) transient following single action potentials for triggering CICR, whereas the priming and inactivation processes of CICR sense a slower, persisting rise in [Ca(2+) ](i) during and after action potential trains. A model is presented that includes CICR activation in elementary units.
authors.affiliation: Department of Physiology, School of Medicine, Nagoya University, Showa-ku, Nagoya, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Soga-Sakakibara
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kubota
authors.forename: Sinichi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tenpei
authors.initials: T
authors.lastname: Akita
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Narita
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuba
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D009046:Motor Neurons / Q000378:metabolism* / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000502:physiology; D011898:Ranidae; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium