Altered properties of quantal neurotransmitter release at endplates of mice lacking P/Q-type Ca2+ channels.
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.
Urbano
Francisco J
FJ
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Piedras-Rentería
Erika S
ES
Jun
Kisun
K
Shin
Hee-Sup
HS
Uchitel
Osvaldo D
OD
Tsien
Richard W
RW
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
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