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.