G(i3) mediates somatostatin-induced activation of an inwardly rectifying K+ current in human growth hormone-secreting adenoma cells

Abstract

SRIF activates an inwardly rectifying K+ current in human GH-secreting adenoma cells. Activation of this K+ current induces hyperpolarization of the membrane and abolishment of action potential firing. This mechanism is an essential mechanism for SRIF-induced decrease in intracellular Ca2+ concentration and inhibition of GH secretion. The activation of the inwardly rectifying K+ current is mediated by a pertussis toxin-sensitive G protein. In this article, the expression of the pertussis toxin-sensitive G protein α-subunits in the human GH-secreting adenoma cells were analyzed by RT-PCR, and the G protein transducing the SRIF-induced activation of this inwardly rectifying K+ current was investigated. RT-PCR of the messenger RNA from two human GH-secreting adenomas revealed that all Gα(i1), Gα(i2), Gα(i3), and Gα(o) were expressed in these adenomas. Primary cultured cells from these two adenoma cells were investigated under the voltage clamp of the whole- cell mode. Specific antibodies against the carboxyl terminus of G protein α- subunits were microinjected into the cells. Microinjection of antibody against the carboxyl terminal sequence of Gα(i3) attenuated the SRIF- induced activation of the inwardly rectifying K+ current, whereas antibody against the common carboxyl terminal sequence of Gα(i1) and Gα(i2) did not. These data indicate that the G protein transducing the SRIF-induced activation of the inwardly rectifying K+ current is G(i3).