title: CaV1.3 as pacemaker channels in adrenal chromaffin cells: specific role on exo- and endocytosis?
abstract: Voltage-gated L-type calcium channels (LTCCs) are expressed in adrenal chromaffin cells. Besides shaping the action potential (AP), LTCCs are involved in the excitation-secretion coupling controlling catecholamine release and in Ca (2+) -dependent vesicle retrieval. Of the two LTCCs expressed in chromaffin cells (CaV1.2 and CaV1.3), CaV1.3 possesses the prerequisites for pacemaking spontaneously firing cells: low-threshold, steep voltage-dependence of activation and slow inactivation. By using CaV1 .3 (-/-) KO mice and the AP-clamp it has been possible to resolve the time course of CaV1.3 pacemaker currents, which is similar to that regulating substantia nigra dopaminergic neurons. In mouse chromaffin cells CaV1.3 is coupled to fast-inactivating BK channels within membrane nanodomains and controls AP repolarization. The ability to carry subthreshold Ca (2+) currents and activate BK channels confers to CaV1.3 the unique feature of driving Ca (2+) loading during long interspike intervals and, possibly, to control the Ca (2+) -dependent exocytosis and endocytosis processes that regulate catecholamine secretion and vesicle recycling.
authors.affiliation: Department of Neuroscience, NIS Centre, Università di Torino, Turin, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Comunanza
authors.forename: Andrea
authors.initials: A
authors.lastname: Marcantoni
authors.forename: David H
authors.initials: DH
authors.lastname: Vandael
authors.forename: Satyajit
authors.initials: S
authors.lastname: Mahapatra
authors.forename: Daniela
authors.initials: D
authors.lastname: Gavello
authors.forename: Valentina
authors.initials: V
authors.lastname: Carabelli
authors.forename: Emilio
authors.initials: E
authors.lastname: Carbone
mesh_terms: D000200:Action Potentials; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks; D020746:Calcium Channels, L-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D019439:Chromaffin Cells / Q000378:metabolism*; D002837:Chromaffin Granules / Q000378:metabolism; D004705:Endocytosis; D005089:Exocytosis; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
chemical_list: C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D002395:Catecholamines; D051036:Large-Conductance Calcium-Activated Potassium Channels