title: Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse.
abstract: Voltage-dependent calcium channels (VDCC) have a key role in neuronal function transforming the voltage signals into intracellular calcium signals. They are composed of the pore-forming alpha(1) and the regulatory alpha(2)delta, gamma and beta subunits. Molecular and functional studies have revealed which alpha(1) subunit gene product is the molecular constituent of each class of native calcium channel (L, N, P/Q, R and T type). Electrophysiological and immunocytochemical studies have suggested that at adult mouse motor nerve terminal (MNT) only P/Q type channels, formed by alpha(1A) subunit, mediate evoked transmitter release. The generation of alpha(1A)-null mutant mice offers an opportunity to study the expression and localization of calcium channels at a synapse with complete loss of P/Q calcium channel. We have investigated the expression and localization of VDCCs alpha(1) and beta subunits at the wild type (WT) and knockout (KO) mouse neuromuscular junction (NMJ) using fluorescence immunocytochemistry. The alpha(1A) subunit was observed only at WT NMJ and was absent at denervated muscles and at KO NMJ. The subunits alpha(1B), alpha(1D) and alpha(1E) were also present at WT NMJ and they were over- expressed at KO NMJ suggesting a compensatory expression due to the lack of the alpha(1A). On the other hand, the beta(1b), beta(2a) and beta(4) were present at the same levels in both genotypes. The presence of other types of VDCC at WT NMJ indicate that they may play other roles in the signaling process which have not been elucidated and also shows that other types of VDCC are able to substitute the alpha(1A) subunit, P/Q channel under certain pathological conditions.
authors.affiliation: Departamento de Fisiología, Biología Celular y Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Pagani
authors.forename: M
authors.initials: M
authors.lastname: Song
authors.forename: M
authors.initials: M
authors.lastname: McEnery
authors.forename: N
authors.initials: N
authors.lastname: Qin
authors.forename: R W
authors.initials: RW
authors.lastname: Tsien
authors.forename: L
authors.initials: L
authors.lastname: Toro
authors.forename: E
authors.initials: E
authors.lastname: Stefani
authors.forename: O D
authors.initials: OD
authors.lastname: Uchitel
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D020864:Calcium Channels, N-Type / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D009469:Neuromuscular Junction / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D009419:Nerve Tissue Proteins; C472073:CACNA1D protein, human; C498916:Cacna1e protein, mouse; C491528:Cacnb2 protein, mouse; C491530:Cacnb4 protein, mouse