We characterized the dependence of the mitogenic response by rabbit corneal epithelial (RCE) cells to serum containing growth factors on K+ channel activation. Using both cell-attached and nystatin-perforated patch-clamp configurations, a K+ channel was identified whose current-voltage relationship is linear with a single-channel conductance of 31 pS. Its activity was barely detectable following 24 h serum starvation. Exposure of starved cells to either 10% FBS, 5 ng/ml epidermal growth factor (EGF) or 2 nM endothelin-1 (ET-1) continuously increased its activity within 30 min by 40%, 54% and 29%, respectively. EGF and ET-1 in combination had additive effects on such activity. Application of 100 µM 4-aminopyridine (4-AP), a K+ channel blocker, inhibited serum-stimulated K+ channel activity by 85%. DNA synthesis was markedly stimulated by serum, whereas incubation with either 4-AP (200 µM) or Ba2+ (1 mM) suppressed this increase by 51% and 23%, respectively, whereas 5 mM tetra ethyl ammonium (TEA) had no effect. Taken together, growth factor-induced increases in proliferation are dependent on K+ channel stimulation. As the increases in K+ channel activity induced by ET-1 and EGF were additive, these mitogens may stimulate K+ channel activity through different signaling pathways linked to their cognate receptors.
The Journal of Membrane Biology – Springer Journals
Published: Jan 1, 2003
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