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1 Laboratoire de Physiologie et Physiopathologie de la Signalisation Cellulaire, CNRS UMR 5543, Université de Bordeaux 2, 33076 Cedex Bordeaux; and 2 Laboratoire d'Immunologie et Cytométrie, Institut Bergonié, 33000 Bordeaux, France
Previously, we showed that the peak density of the transient outward K+ current (Ito) 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 Ito drops precisely at the quiescent (G0 phase)/proliferating transition. This change is not due to a modification in the voltage dependence of Ito, but rather to a modification in its inactivation kinetics. Molecular determination of K+ channel subunits showed that Ito required the expression of Kv1.4, Kv4.1, and Kv4.3. We found that the increase in Ito 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 Ito expression and cell proliferation is not mediated by variations in cell excitability. These results provide new evidence for the cell cycle dependence of Ito expression, which could be relevant in understanding the mechanisms leading to pituitary adenomas.
Kv1.4; cell growth; excitable cell; transient outward K+ current
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