title: Ca(v)1.3 and BK channels for timing and regulating cell firing.
abstract: L-type Ca(2+) channels (LTCCs, Ca(v)1) open readily during membrane depolarization and allow Ca(2+) to enter the cell. In this way, LTCCs regulate cell excitability and trigger a variety of Ca(2+)-dependent physiological processes such as: excitation-contraction coupling in muscle cells, gene expression, synaptic plasticity, neuronal differentiation, hormone secretion, and pacemaker activity in heart, neurons, and endocrine cells. Among the two major isoforms of LTCCs expressed in excitable tissues (Ca(v)1.2 and Ca(v)1.3), Ca(v)1.3 appears suitable for supporting a pacemaker current in spontaneously firing cells. It has steep voltage dependence and low threshold of activation and inactivates slowly. Using Ca(v)1.3(-/-) KO mice and membrane current recording techniques such as the dynamic and the action potential clamp, it has been possible to resolve the time course of Ca(v)1.3 pacemaker currents that regulate the spontaneous firing of dopaminergic neurons and adrenal chromaffin cells. In several cell types, Ca(v)1.3 is selectively coupled to BK channels within membrane nanodomains and controls both the firing frequency and the action potential repolarization phase. Here we review the most critical aspects of Ca(v)1.3 channel gating and its coupling to large conductance BK channels recently discovered in spontaneously firing neurons and neuroendocrine cells with the aim of furnishing a converging view of the role that these two channel types play in the regulation of cell excitability.
authors.affiliation: Department of Neuroscience, NIS Centre, CNISM, Corso Raffaello 30, 10125 Turin, Italy.
authors.forename: David Henry
authors.initials: DH
authors.lastname: Vandael
authors.forename: Andrea
authors.initials: A
authors.lastname: Marcantoni
authors.forename: Satyajit
authors.initials: S
authors.lastname: Mahapatra
authors.forename: Anton
authors.initials: A
authors.lastname: Caro
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zuccotti
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Emilio
authors.initials: E
authors.lastname: Carbone
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D019439:Chromaffin Cells / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
chemical_list: C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D051036:Large-Conductance Calcium-Activated Potassium Channels