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Ca2+/calmodulin binds to and modulates P/Q-type calcium channels

Nature volume 399, pages 155–159 (1999)Cite this article

Abstract

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels1,2, which are densely localized in nerve terminals3. Because neurotransmitter release is proportional to the fourth power of calcium concentration4,5, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins6,7, and recent evidence indicates feedback regulation of P/Q-type channels by calcium8. Although calcium-dependent inactivation of L-type channels is well documented9,10,11, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the α1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.

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Figure 1: Calmodulin binding to the C-terminal domain of the α1A subunit.
Figure 2: Ca2+-dependent binding of calmodulin to α1A.
Figure 3: Effects of Ca2+ and calmodulin on inactivation of P/Q-type channels.
Figure 4: Effects of Ca2+ and calmodulin on recovery from inactivation.

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Acknowledgements

We thank T. Snutch, M. Harpold and K. Campbell for cDNAs encoding Ca2+-channel subunits. This work was supported by an NRSA postdoctoral fellowship from the NIH to A.L. and by research grants from the NIH to D.R.S. and W.A.C.

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Authors and Affiliations

  1. Department of Pharmacology, University of Washington, Seattle, 98195-7280, Washington, USA

    Amy Lee, Scott T. Wong, Daniel Gallagher, Bin Li, Daniel R. Storm, Todd Scheuer & William A. Catterall

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  1. Amy Lee
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Correspondence to William A. Catterall.

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Lee, A., Wong, S., Gallagher, D. et al. Ca2+/calmodulin binds to and modulates P/Q-type calcium channels. Nature 399, 155–159 (1999). https://doi.org/10.1038/20194

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