Growth factor-mediated K+ channel activity associated with human myeloblastic ML-1 cell proliferation.

ML-1 cell proliferation is dependent on the presence of serum growth factors. Removing serum from the culture medium results in growth arrest and promotes differentiation. In this study, we found that a 4-aminopyridine-sensitive K+ channel was highly expressed in proliferating ML-1 cells and significantly diminished in G1-arrested ML-1 cells induced by serum deprivation but was restored within 30 min in these cells with addition of 10% fetal bovine serum (FBS) or 5 ng/ml epidermal growth factor (EGF). Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels, but not guanosine 3',5'-cyclic monophosphate, were significantly increased in serum-deprived cells stimulated by FBS or EGF, and the effects of FBS and EGF on the channel activation were mimicked by exogenous cAMP. In inside-out patches, K+ channel activity was significantly increased by the cAMP-dependent protein kinase catalytic subunit, whereas the effect of EGF on K+ channel activation was blocked by Rp-8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphothioate. Together, our results demonstrate that serum growth factors stimulate K+ channel activity in proliferation of ML-1 cells through protein kinase-induced phosphorylation and suggest an important molecular mechanism for serum growth factor-stimulated mitogenesis in ML-1 cells.