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cDNA cloning and functional characterization of the mouse Ca2+-gated K+ channel, mIK1. Roles in regulatory volume

D H Vandorpe1, B E Shmukler, L Jiang

  • 1Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center Boston, Massachusetts 02215, USA.

The Journal of Biological Chemistry
|August 15, 1998
PubMed
Summary

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We identified the mIK1 calcium-gated potassium channel in mouse cells. Its expression in oocytes enabled a novel volume decrease response, and clotrimazole inhibited stem cell proliferation.

Area of Science:

  • Molecular Biology
  • Cell Physiology
  • Ion Channel Research

Background:

  • The Ca2+-gated K+ (KCa) channel, hIK1, is crucial in various cell types.
  • Understanding mammalian KCa channels is vital for cellular function and disease research.

Purpose of the Study:

  • To clone and characterize the mouse homolog of hIK1, named mIK1.
  • To investigate the functional properties and physiological roles of the mIK1 channel.

Main Methods:

  • Cloning of mIK1 cDNA from murine erythroleukemia (MEL) cells, thymus, and stomach.
  • Expression of mIK1 in Xenopus oocytes for electrophysiological analysis.
  • Assessing mIK1 channel activity, Ca2+ dependence, and pharmacological properties.
  • Investigating the role of mIK1 in oocyte regulatory volume decrease and stem cell differentiation.

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Main Results:

  • mIK1 mRNA is expressed in multiple mouse tissues.
  • Expressed mIK1 channels exhibit properties similar to red blood cell (Gardos) and MEL cell KCa channels.
  • mIK1 expression in oocytes confers a Ca2+-dependent, clotrimazole-sensitive regulatory volume decrease.
  • Low nanomolar clotrimazole concentrations inhibit stem cell proliferation and erythroid differentiation.

Conclusions:

  • mIK1 is a functional Ca2+-gated K+ channel in mice with characteristics similar to known erythroid KCa channels.
  • mIK1 plays a role in cellular volume regulation and is a potential target for modulating stem cell proliferation and differentiation.