SELECTIVE G-PROTEIN REGULATION OF NEURONAL CALCIUM CHANNELS

Citation
Pt. Toth et al., SELECTIVE G-PROTEIN REGULATION OF NEURONAL CALCIUM CHANNELS, The Journal of neuroscience, 16(15), 1996, pp. 4617-4624
Citations number
53
Categorie Soggetti
Neurosciences,Neurosciences
Journal title
ISSN journal
02706474
Volume
16
Issue
15
Year of publication
1996
Pages
4617 - 4624
Database
ISI
SICI code
0270-6474(1996)16:15<4617:SGRONC>2.0.ZU;2-V
Abstract
We examined the properties and regulation of Ca channels resulting fro m the expression of human alpha(1B) and alpha(1E) subunits stably expr essed in HEK293 cells. The ancillary subunits beta(1B) and alpha(2)/de lta were also stably expressed in these cell lines. Ca currents in alp ha(1B)-expressing cells had the properties of N-type currents. Ca curr ents in cells expressing alpha(1E) exhibited a novel profile that was similar to the properties of the ''R type'' Ca current. Introduction o f GTP-gamma-S into alpha(1B) cells greatly enhanced the extent of prep ulse facilitation of the Ca current, whereas it had only a very small effect in alpha(1E)-expressing cells. Activation of somatostatin recep tors endogenous to HEK293 cells or kappa opioid receptors, expressed i n the cells after transfection, inhibited Ca currents in alpha(1B)-exp ressing cells. This inhibition was blocked by pertussis toxin and was partially relieved by a depolarizing prepulse. In contrast, no inhibit ory effects were noted in cells expressing alpha(1E) channels under th e same circumstances. HEK293 cells normally contained G-proteins from all of the four major families. Inhibition of Ca currents by kappa ago nists in alpha(1E)-expressing cells was enhanced slightly by the cotra nsfection of several G-protein a subunits. kappa agonists, however, ha d no effect in alpha(1E)-containing cells, even after overexpression o f different G-protein alpha-subunits. In summary, these results demons trate that there is a large difference in the susceptibility of alpha( 1B)- and alpha(1E)-based Ca channels to regulation by G-proteins. This is so despite the fact that the two types of Ca channels show substan tial similarities in their primary sequences.