title: Ryanodine facilitates calcium-dependent release of transmitter at mouse neuromuscular junctions.
abstract: 1. Quantal release of transmitter was measured intracellularly at mouse neuromuscular junctions in the presence and absence of ryanodine (Rnd). 2. Rnd at concentrations up to 1 microM did not significantly alter the frequency of miniature endplate potentials (m.e.p.ps) in the presence or absence of Ca2+, suggesting that Rnd is unlikely to alter the internal concentration of Ca2+ ([Ca2+]i) at rest. 3. In a high-K+ (10 mM) bathing solution, Rnd further potentiated the facilitatory effect of Ca2+ on the frequency (F, s-1) of m.e.p.ps. Rnd shifted the relationship between 1n(F) and 1n[Ca2+]o to lower concentrations. 4. In a high-Mg2+ bathing solution, Rnd did not affect the frequency of m.e.p.ps at any value of [Ca2+]o. However, Rnd slightly but significantly increased the quantal content (m) of e.p.ps. It shifted the relationship between 1n(m) and 1n[Ca2+]o to lower concentrations. These results suggest that Rnd potentiates the quantal release of transmitter after depolarization of the membrane or nerve impulse, in keeping with the cooperativity of Ca2+ at the active site. 5. A series of two closely spaced nerve impulses produced a facilitation of transmitter release, as judged by the quantal content (m2) of the second response in relation to that of the first one (m1), m2/m1. Rnd did not change the ratio m2/m1. Thus Rnd is unlikely to affect the rapid phase of the sequestration of Ca2+ inside the nerve terminal. 6. High levels of K+ (5 mM) and caffeine (2 mM) potentiated both modes of transmitter release, in a manner dependent on [Ca2+]o. Caffeine did not potentiate facilitation of transmitter release. 7. These results indicate that Rnd facilitates the quantal release of transmitter presumably via an increase in [Ca2 ]i by a manner different from that of high-K+ or caffeine. The results suggest that Rnd probably affects calcium turnover in neuronal cells.
authors.affiliation: Department of Veterinary Pharmacology, College of Agriculture, University of Osaka Prefecture, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Tsubaki
authors.forename: O
authors.initials: O
authors.lastname: Yagasaki
authors.forename: K
authors.initials: K
authors.lastname: Ito
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D012132:Respiratory Muscles / Q000187:drug effects / Q000294:innervation; D012433:Ryanodine / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D018377:Neurotransmitter Agents; D012433:Ryanodine; D002110:Caffeine; D011188:Potassium; D002118:Calcium