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

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Several human channelopathies result from mutations in α 1A, the pore-forming subunit of P/Q-type Ca2+ channels, conduits of presynaptic Ca2+ entry for evoked neurotransmission. We found that wild-type human α1A subunits supported transmission between cultured mouse hippocampal neurons equally well as endogenous mouse α1A, whereas introduction of impermeant human α1A 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 α1A 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.

Original languageEnglish (US)
Pages (from-to)387-400
Number of pages14
JournalNeuron
Volume43
Issue number3
DOIs
StatePublished - Aug 5 2004

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Channelopathies
Synaptic Transmission
Neurons
Mutation
Familial type 1 Hemiplegic migraine

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Cao, Yu Qing ; Piedras-Rentería, Erika S. ; Smith, Geoffrey B. ; Chen, Gong ; Harata, Nobutoshi C. ; Tsien, Richard W. / Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy. In: Neuron. 2004 ; Vol. 43, No. 3. pp. 387-400.
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Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy. / Cao, Yu Qing; Piedras-Rentería, Erika S.; Smith, Geoffrey B.; Chen, Gong; Harata, Nobutoshi C.; Tsien, Richard W.

In: Neuron, Vol. 43, No. 3, 05.08.2004, p. 387-400.

Research output: Contribution to journalArticle

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