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J Neurophysiol 92: 2633-2641, 2004; doi:10.1152/jn.00486.2004
0022-3077/04 $5.00
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REVIEW

L-Type Calcium Channels: The Low Down

Diane Lipscombe, Thomas D. Helton and Weifeng Xu

Department of Neuroscience, Brown University, Providence, Rhode Island 02912

Submitted 9 May 2004; accepted in final form 5 June 2004

ABSTRACT

L-type calcium channels couple membrane depolarization in neurons to numerous processes including gene expression, synaptic efficacy, and cell survival. To establish the contribution of L-type calcium channels to various signaling cascades, investigators have relied on their unique pharmacological sensitivity to dihydropyridines. The traditional view of dihydropyridine-sensitive L-type calcium channels is that they are high-voltage–activating and have slow activation kinetics. These properties limit the involvement of L-type calcium channels to neuronal functions triggered by strong and sustained depolarizations. This review highlights literature, both long-standing and recent, that points to significant functional diversity among L-type calcium channels expressed in neurons and other excitable cells. Past literature contains several reports of low-voltage–activated neuronal L-type calcium channels that parallel the unique properties of recently cloned CaV1.3 L-type channels. The fast kinetics and low activation thresholds of CaV1.3 channels stand in stark contrast to criteria currently used to describe L-type calcium channels. A more accurate view of neuronal L-type calcium channels encompasses a broad range of activation thresholds and recognizes their potential contribution to signaling cascades triggered by subthreshold depolarizations.

Address for reprint requests and other correspondence: D. Lipscombe, Department of Neuroscience, Brown University, 190 Thayer Street, Providence, RI 02912 (E-mail: diane_lipscombe{at}brown.edu).




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