title: Ca(2+)-dependent activation of T-type Ca2+ channels by calmodulin-dependent protein kinase II.
abstract: The T-type Ca2+ channel is unique among voltage-dependent Ca2+ channels in its low threshold for opening and its slow kinetics of deactivation. Here, we evaluate the importance of intracellular Ca2+ (Cai2+) in promoting low-threshold gating of T-type channels in adrenal glomerulosa cells. We observe that 390 nM to 1.27 microM Cai2+ enhances T-type current by shifting the voltage dependence of channel activation to more negative potentials. This Ca(2+)-induced shift is mediated by calmodulin-dependent protein kinase II (CaMKII), because it is abolished by inhibitors of CaMKII but not of protein kinase C and is subsequently restored by exogenous calmodulin. This Ca(2+)-induced reduction in gating threshold would render T-type Ca2+ channels uniquely suited to transduce depolarizing stimuli of low amplitude into a Ca2+ signal sufficient to support a physiological response.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville 22908.
authors.forename: H K
authors.initials: HK
authors.lastname: Lu
authors.forename: R J
authors.initials: RJ
authors.lastname: Fern
authors.forename: J J
authors.initials: JJ
authors.lastname: Nee
authors.forename: P Q
authors.initials: PQ
authors.lastname: Barrett
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D004594:Electrophysiology; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism / Q000502:physiology
chemical_list: D015220:Calcium Channels; D007546:Isoquinolines; D010879:Piperazines; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium