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Splicing of α1A subunit gene generates phenotypic variants of P- and Q-type calcium channels

Nature Neuroscience volume 2, pages 407–415 (1999)Cite this article

Abstract

P-type and Q-type calcium channels mediate neurotransmitter release at many synapses in the mammalian nervous system. The α1A calcium channel has been implicated in the etiologies of conditions such as episodic ataxia, epilepsy and familial migraine, and shares several properties with native P- and Q-type channels. However, the exact relationship between α1A and P- and Q-type channels is unknown. Here we report that alternative splicing of the α1A subunit gene results in channels with distinct kinetic, pharmacological and modulatory properties. Overall, the results indicate that alternative splicing of the α1A gene generates P-type and Q-type channels as well as multiple phenotypic variants.

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Figure 1: Alternative splicing generates multiple α1A isoforms.
Figure 2: Both α1A-a and α1A-b variants are expressed in the rat nervous system.
Figure 3: α1A-a and α1A-b have distinct functional properties.
Figure 4: Splicing of the domain I–II linker and domain IV S3–S4 loop make distinct contributions to channel kinetics and gating.
Figure 5: Sensitivities of α1A-a and α1A-a (+NP) to ω-Aga-IVA and ω-CTx-MVIIC.
Figure 6: Differential modulation of α1A splice variants by G proteins and PKC.

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Acknowledgements

We thank M. Gilbert and A. Stea for comments, E. Perez-Reyes for β2a and β4 subunit cDNAs, and M. Ahlijanian (Pfizer) for ω-agatoxin IVA. T.W.S. was supported by a fellowship from the University of Singapore, Institute of Molecular Biology, E.B. by fellowships from INSERM and EMBO, K.S. by a grant from the Amytrophic Lateral Sclerosis Society of Canada, G.W.Z .by a grant from the Medical Research Council (MRC) of Canada and scholarships from MRC and the Alberta Heritage Foundation for Medical Research. E.B. and G.W.Z. are supported by NATO grant (CRG 971546) and T.P.S. is supported by a grant from the MRC of Canada and an MRC Scientist award.

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Author notes

  1. Tuck W. Soong

    Present address: Institute of Molecular and Cell Biology, University of Singapore, 30 Medical Drive, Singapore

  2. Emmanuel Bourinet and Tuck W. Soong: The first two authors contributed equally to this work

Authors and Affiliations

  1. Physiopathologie des Canaux Ioniques, IGH, CNRS UPR 1142, Montpellier, France

    Emmanuel Bourinet, Arnaud Monteil & Joel Nargeot

  2. Biotechnology Laboratory, University of British Columbia,, Vancouver, British Columbia, Canada

    Tuck W. Soong, Kathy Sutton, Sarah Slaymaker, Eleanor Mathews & Terry P. Snutch

  3. Department of Pharmacology, University of Calgary, Calgary, Alberta, Canada

    Gerald W. Zamponi

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Bourinet, E., Soong, T., Sutton, K. et al. Splicing of α1A subunit gene generates phenotypic variants of P- and Q-type calcium channels. Nat Neurosci 2, 407–415 (1999). https://doi.org/10.1038/8070

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