Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy

Yu-Qing Cao; Erika S Piedras-Rentería; Geoffrey B Smith; Gong Chen; Nobutoshi C Harata; Richard W Tsien

doi:10.1016/j.neuron.2004.07.014

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Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy

Journal article

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Peer reviewed

Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy

Yu-Qing Cao, Erika S Piedras-Rentería, Geoffrey B Smith, Gong Chen, Nobutoshi C Harata and Richard W Tsien

Neuron (Cambridge, Mass.), Vol.43(3), pp.387-400

08/05/2004

DOI: 10.1016/j.neuron.2004.07.014

PMID: 15294146

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Abstract

Several human channelopathies result from mutations in alpha1A, the pore-forming subunit of P/Q-type Ca2+ channels, conduits of presynaptic Ca2+ entry for evoked neurotransmission. We found that wild-type human alpha1A subunits supported transmission between cultured mouse hippocampal neurons equally well as endogenous mouse alpha1A, whereas introduction of impermeant human alpha1A hampered the effect of endogenous subunits. Thus, presynaptic P/Q-type channels may compete for channel type-preferring "slots" that limit their synaptic effectiveness. The existence of slots generates predictions for how neurotransmission might be affected by changes in Ca2+ channel properties, which we tested by studying alpha1A mutations that are associated with familial hemiplegic migraine type 1 (FHM1). Mutant human P/Q-type channels were impaired in contributing to neurotransmission in precise accord with their deficiency in supporting whole-cell Ca2+ channel activity. Expression of mutant channels in wild-type neurons reduced the synaptic contribution of P/Q-type channels, suggesting that competition for type-preferring slots might support the dominant inheritance of FHM1.

Calcium Channels, P-Type

Cell Line

Migraine with Aura - metabolism

Synaptic Transmission - physiology

Synaptic Transmission - genetics

Humans

Cells, Cultured

Presynaptic Terminals - physiology

Calcium Channels, Q-Type

Excitatory Postsynaptic Potentials - physiology

Hippocampus - metabolism

Calcium Channels - physiology

Animals

Calcium Channels, N-Type

Migraine with Aura - physiopathology

Calcium Channels - biosynthesis

Mice

Neurons - metabolism

Migraine with Aura - genetics

Mutation

Calcium Channels - genetics

Details

Title: Subtitle: Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy
Creators: Yu-Qing Cao - Department of Molecular and Cellular Physiology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305, USA
Erika S Piedras-Rentería
Geoffrey B Smith
Gong Chen
Nobutoshi C Harata
Richard W Tsien
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.43(3), pp.387-400
Publisher: United States
DOI: 10.1016/j.neuron.2004.07.014
PMID: 15294146
ISSN: 0896-6273
eISSN: 1097-4199
Grant note: NS24067 / NINDS NIH HHS
Language: English
Date published: 08/05/2004
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984025678502771

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