title: Altered properties of quantal neurotransmitter release at endplates of mice lacking P/Q-type Ca2+ channels.
abstract: Transmission at the mouse neuromuscular junction normally relies on P/Q-type channels, but became jointly dependent on both N- and R-type Ca(2+) channels when the PQ-type channel alpha(1A) subunit was deleted. R-type channels lay close to Ca(2+) sensors for exocytosis and I(K(Ca)) channel activation, like the P/Q-type channels they replaced. In contrast, N-type channels were less well localized, but abundant enough to influence secretion strongly, particularly when action potentials were prolonged. Our data suggested that active zone structures may select among multiple Ca(2+) channels in the hierarchy P/Q >R >N. The alpha(1A)-/- neuromuscular junction displayed several other differences from wild-type: lowered quantal content but greater ability to withstand reductions in the Ca(2+)/Mg(2+) ratio, and little or no paired-pulse facilitation, the latter findings possibly reflecting compensatory mechanisms at individual release sites. Changes in presynaptic function were also associated with a significant reduction in the size of postsynaptic acetylcholine receptor clusters.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Urbano
authors.forename: Erika S
authors.initials: ES
authors.lastname: Piedras-Rentería
authors.forename: Kisun
authors.initials: K
authors.lastname: Jun
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Osvaldo D
authors.initials: OD
authors.lastname: Uchitel
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsien
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D020864:Calcium Channels, N-Type / Q000502:physiology; D020865:Calcium Channels, P-Type / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D020908:Calcium Channels, R-Type / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020908:Calcium Channels, R-Type; D018377:Neurotransmitter Agents; D015761:4-Aminopyridine