cDNA cloning and functional characterization of the mouse Ca²⁺-gated K⁺ channel, mIK1

We have cloned from murine erythroleukemia (MEL) cells, thymus, and stomach the cDNA encoding the Ca²⁺-gated K⁺ (K(Ca)) channel, mIK1, the mouse homolog of hIK1 (Ishii, T. M., Silvia, C., Hirschberg, B., Bond, C. T., Adelman, J.P., and Maylie, J. (1997) Proc. Natl. Acad. Sci.(U.S.A. 94, 11651- 11656). mIK1 mRNA was detected at varied levels in many tissue types. mIK1 K(Ca) channel activity expressed in Xenopus oocytes closely resembled the K(ca) of red cells (Gardos channel) and MEL cells in its single channel conductance, lack of voltage-sensitivity of activation, inward rectification, and Ca²⁺ concentration dependence, mIK1 also resembled the erythroid channel in its pharmacological properties, mediating whole cell and unitary currents sensitive to low nM concentrations of both clotrimazole (CLT) and its des-imidazolyl metabolite, 2-chlorophenyl-bisphenyl-methanol, and to low nm concentrations of iodocharybdotoxin. Whereas control oocytes subjected to hypotonic swelling remained swollen, mIK1 expression conferred on oocytes a novel, Ca²⁺-dependent, CLT-sensitive regulatory volume decrease response. Hypotonic swelling of voltage-clamped mIK1-expressing oocytes increased outward currents that were Ca²⁺-dependent, CLT-sensitive, and reversed near the K⁺ equilibrium potential. mIK1 mRNA levels in ES cells increased steadily during erythroid differentiation in culture, in contrast to other K(Ca) mRNAs examined. Low nanomolar concentrations of CLT inhibited proliferation and erythroid differentiation of peripheral blood stem cells in liquid culture.