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J. Biol. Chem., Vol. 279, Issue 39, 41157-41167, September 24, 2004

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Uncoupling of Calcium Channel ₁ and Subunits in Developing Neurons^*

J. David Spafford, Jan van Minnen, Peter Larsen¶, August B. Smit, Naweed I. Syed||**, and Gerald W. Zamponi||

From the Cellular and Molecular Neurobiology Research Group, University of Calgary, Calgary T2N 4N1, Canada, the Department of Molecular and Cellular Neurobiology, Research Institute Neurosciences, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands, and the ^¶Department of Clinical Neurosciences, University of Calgary, Calgary T2N 4N1, Canada

Calcium channel subunits are key modulators of calcium channel function and membrane targeting of the pore-forming ₁ subunit. Here we show that an invertebrate (Lymnaea stagnalis) homolog of P/Q- and N-type calcium channels (LCa_v2), although colocalized with subunits in synapses of mature neurons, is physically uncoupled from the subunits in the leading edge of growth cones of outgrowing neurons. Moreover, LCa_v2 channels that mediate transmitter release in mature synapses also participate in neuronal outgrowth in growth cones. The differential association of subunits with synaptic calcium channels and those expressed in emergent neuronal growth suggests that subunits may play a role in the transformation of Ca_v2 calcium channel function in immature neurons and mature synapses.

Received for publication, April 5, 2004 , and in revised form, July 16, 2004.

^* This work was supported in part by operating grants from the Canadian Institutes of Health Research (to G. W. Z. and N. I. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| Canadian Institutes of Health Research Investigator.

^** Recipient of a Scientist award from the Alberta Heritage Foundation for Medical Research.

Recipient of Senior Scholar award from the Alberta Heritage Foundation for Medical Research, a Canada Research Chair award, and an Independent Investigator award from the National Alliance for Research on Schizophrenia and Depression. To whom for correspondence should be addressed: Dept. of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. NW, Calgary T2N 4N1, Canada. Tel.: 403-220-8687; Fax: 403-210-8106; E-mail: Zamponi{at}ucalgary.ca.

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