Ca2+ channels and synaptic transmission at the adult, neonatal, and P/Q-type deficient neuromuscular junction.
Different types of voltage-activated Ca(2+) channels have been established based on their molecular structure and pharmacological and biophysical properties. One of them, the P/Q-type, is the main channel involved in nerve-evoked neurotransmitter release at neuromuscular junctions and the immunological target in Eaton-Lambert Syndrome. At adult neuromuscular junctions, L- and N-type Ca(2+) channels become involved in transmitter release only under certain experimental or pathological conditions. In contrast, at neonatal rat neuromuscular junctions, nerve-evoked synaptic transmission depends jointly on both N- and P/Q-type channels. Synaptic transmission at neuromuscular junctions of the ataxic P/Q-type Ca(2+) channel knockout mice is also dependent on two different types of channels, N- and R-type. At both neonatal and P/Q knockout junctions, the K(+)-evoked increase in miniature endplate potential frequency was not affected by N-type channel blockers, but strongly reduced by both P/Q- and R-type channel blockers. These differences could be accounted for by a differential location of the channels at the release site, being either P/Q- or R-type Ca(2+) channels located closer to the release site than N-type Ca(2+) channels. Thus, Ca(2+) channels may be recruited to mediate neurotransmitter release where P/Q-type channels seem to be the most suited type of Ca(2+) channel to mediate exocytosis at neuromuscular junctions.
Nudler
Silvana
S
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IFIBYNE-CONICET, Buenos Aires, Argentina.
Piriz
Joaquin
J
Urbano
Francisco J
FJ
Rosato-Siri
Marcelo D
MD
Renteria
Erika S Piedras
ES
Uchitel
Osvaldo D
OD
D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000145:classification / Q000172:deficiency / Q000502:physiology*; D005333:Fetus; D006801:Humans; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020511:Neuromuscular Junction Diseases / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D018377:Neurotransmitter Agents; D011188:Potassium