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Issue 998 coverMYASTHENIA GRAVIS AND RELATED DISORDERS: Biochemical Basis for Disease of the Neuromuscular Junction Volume 998 published September 2003
Ann. N.Y. Acad. Sci. 998: 11 (2003). doi: 10.1196/annals.1254.003
Copyright © 2003 by the New York Academy of Sciences
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Articles by NUDLER, S.
Articles by UCHITEL, O. D.
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Articles by NUDLER, S.
Articles by UCHITEL, O. D.
Ca2+ Channels and Synaptic Transmission at the Adult, Neonatal, and P/Q-Type Deficient Neuromuscular Junction

SILVANA NUDLERa, JOAQUIN PIRIZa, FRANCISCO J. URBANOa,b, MARCELO D. ROSATO-SIRIa,c, ERIKA S. PIEDRAS RENTERIAd,e AND OSVALDO D. UCHITELa,f

aLaboratorio 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
dDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, California, USA

bPresent address: Department of Physiology and Neuroscience, NYU School of Medicine, 550 First Avenue, New York, NY 10016.
cPresent address: Biophysics Sector, S.I.S.S.A./I.S.A.S., Via Beirut 2-4, 34014 Trieste, Italy.
ePresent address: Department of Physiology, Loyola University Chicago, Maywood, IL 60153.
fAddress for correspondence: Osvaldo D. Uchitel, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II piso 2, Buenos Aires 1428, Argentina. Voice: +54 11 4576 3368; fax: +54 11 4576 3321.
odu{at}fbmc.fcen.uba.ar
Ann. N.Y. Acad. Sci. 998: 11-17 (2003).

Different types of voltage-activated Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ channels located closer to the release site than N-type Ca2+ channels. Thus, Ca2+ channels may be recruited to mediate neurotransmitter release where P/Q-type channels seem to be the most suited type of Ca2+ channel to mediate exocytosis at neuromuscular junctions.

Key Words: calcium channels • neuromuscular junction • transmitter release • miniature endplate potentials • calcium dependence




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