L-type calcium channels: the low down.
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.
Lipscombe
Diane
D
Department of Neuroscience, Brown University, 190 Thayer Street, Providence, RI 02912, USA. diane_lipscombe@brown.edu
Helton
Thomas D
TD
Xu
Weifeng
W
D000818:Animals; D020746:Calcium Channels, L-Type / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000502:physiology*
D020746:Calcium Channels, L-Type