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.