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

David H. Vandorpe, Boris E. Shmukler, Lianwei Jiang, Bing Lim, James Maylie, John P. Adelman, Lucia De Franceschi, M. Domenica Cappellini, Carlo Brugnara, Seth L. Alper

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21542-21553
Number of pages12
JournalJournal of Biological Chemistry
Volume273
Issue number34
DOIs
StatePublished - Aug 21 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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