L-type calcium channels: the low down

D Lipscombe, TD Helton, W Xu - Journal of …, 2004 - journals.physiology.org
D Lipscombe, TD Helton, W Xu
Journal of neurophysiology, 2004journals.physiology.org
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 …
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.
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