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Neurotransmitter release from tottering mice nerve terminals with reduced expression of mutated P‐ and Q‐type Ca 2+ ‐channels
Author(s) -
Leenders A. G. Miriam,
Van Den Maagdenberg Arn M. J. M.,
Da Silva Fernando H. Lopes,
Sheng ZuHang,
Molenaar Peter C.,
Ghijsen Wim E. J. M.
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01839.x
Subject(s) - glutamate receptor , neurotransmitter , voltage dependent calcium channel , depolarization , protein subunit , biology , medicine , calcium channel , endocrinology , cholecystokinin , neuroscience , chemistry , calcium , biochemistry , central nervous system , receptor , gene
Neurotransmitter release is triggered by Ca 2+ ‐influx through multiple sub‐types of high voltage‐activated Ca 2+ ‐channels. Tottering mice have a mutation in the α1A pore‐forming subunit of P‐ and Q‐type Ca 2+ ‐channels, two prominent sub‐types that regulate transmitter release from central nerve terminals. Immunoblotting analysis of purified forebrain terminals from tottering mice revealed an 85% reduction in the protein expression level of the mutated α1A subunit compared to expression of the α1A subunit in wild‐type terminals. In contrast, the expression of the α1B subunit of the N‐type Ca 2+ ‐channels was unchanged. Release of the amino acids glutamate and GABA and of the neuropeptide cholecystokinin (CCK) induced by a short (100 ms) depolarization pulse was unchanged in the terminals of tottering mice. Studies using specific blockers of Ca 2+ ‐channels however, revealed a reduced contribution of P‐ and Q‐type Ca 2+ ‐channels to glutamate and cholecystokinin release, whereas a greater reliance on N‐type Ca 2+ ‐channels for release of these transmitters was observed. In contrast, the contribution of the P‐, Q‐ and N‐type Ca 2+ ‐channels to the release of GABA was not altered in tottering mice. These results indicate that the expression of the α1A subunit was decreased in terminals from tottering mice, and that a decreased contribution of P‐ and Q‐type Ca 2+ ‐channels to the release of glutamate and cholecystokinin was functionally compensated by an increased contribution of N‐type Ca 2+ ‐channels.