title: Selective G-protein regulation of neuronal calcium channels.
abstract: We examined the properties and regulation of Ca channels resulting from the expression of human alpha1B and alpha1E subunits stably expressed in KEK293 cells. The ancillary subunits beta1B and alpha2/delta were also stably expressed in these cell lines. Ca currents in alpha1B-expressing cells had the properties of N-type currents. Ca currents in cells expressing alpha1E exhibited a novel profile that was similar to the properties of the "R type" Ca current. Introduction of GTP-gamma-S into alpha1B cells greatly enhanced the extent of prepulse facilitation of the Ca current, whereas it had only a very small effect in alpha1E-expressing cells. Activation of somatostatin receptors endogenous to HEK293 cells or kappa opioid receptors, expressed in the cells after transfection, inhibited Ca currents in alpha1B-expressing cells. This inhibition was blocked by pertussis toxin and was partially relieved by a depolarizing prepulse. In contrast, no inhibitory effects were noted in cells expressing alpha1E channels under the same circumstances. HEK293 cells normally contained G-proteins from all of the four major families. Inhibition of Ca currents by kappa agonists in alpha1B-expressing cells was enhanced slightly by the cotransfection of several G-protein alpha subunits. kappa agonists, however, had no effect in alpha1E-containing cells, even after overexpression of different G-protein alpha-subunits. In summary, these results demonstrate that there is a large difference in the susceptibility of alpha1B- and alpha1E-based Ca channels to regulation by G-proteins. This is so despite the fact that the two types of Ca channels show substantial similarities in their primary sequences.
authors.affiliation: Department of Pharmacological and Physiological Sciences, The University of Chicago, Illinois 60637, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Toth
authors.forename: L R
authors.initials: LR
authors.lastname: Shekter
authors.forename: G H
authors.initials: GH
authors.lastname: Ma
authors.forename: L H
authors.initials: LH
authors.lastname: Philipson
authors.forename: R J
authors.initials: RJ
authors.lastname: Miller
mesh_terms: D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D018408:Patch-Clamp Techniques; D013004:Somatostatin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D013004:Somatostatin; D019204:GTP-Binding Proteins