Potassium channel expression level is dependent on the proliferation state in the GH3 pituitary cell line

Previously, we showed that the peak density of the transient outward K(+) current (I(to)) expressed in GH3 cells was different in the S phase than in other phases of the cell cycle. Using cell synchronization, we show here that I(to) drops precisely at the quiescent (G(0) phase)/proliferating transition. This change is not due to a modification in the voltage dependence of I(to), but rather to a modification in its inactivation kinetics. Molecular determination of K(+) channel subunits showed that I(to) required the expression of Kv1.4, Kv4.1, and Kv4.3. We found that the increase in I(to) density during the quiescent state was accompanied by an increase in Kv1.4 protein expression, whereas Kv4.3 expression remained unchanged. We further demonstrate that the link between I(to) expression and cell proliferation is not mediated by variations in cell excitability. These results provide new evidence for the cell cycle dependence of I(to) expression, which could be relevant in understanding the mechanisms leading to pituitary adenomas.