Regulation of Transient Receptor Potential Melastatin 7 (TRPM7) Currents by Mitochondria

  • Kim, Byung Joo (Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine) ;
  • Jeon, Ju-Hong (Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Seon Jeong (Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University) ;
  • So, Insuk (Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Ki Whan (Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine)
  • Received : 2006.08.30
  • Accepted : 2007.03.16
  • Published : 2007.06.30

Abstract

Mitochondria play a central role in energy-generating processes and may be involved in the regulation of channels and receptors. Here we investigated TRPM7, an ion channel and functional kinase, and its regulation by mitochondria. Proton ionophores such as CCCP elicited a rapid decrease in outward TRPM7 whole-cell currents but a slight increase in inward currents with pipette solutions containing no MgATP. With pipette solutions containing 3 mM MgATP, however, CCCP increased both outward and inward TRPM7 currents. This effect was reproducible and fully reversible, and repeated application of CCCP yielded similar decreases in current amplitude. Oligomycin, an inhibitor of $F_1/F_O$-ATP synthase, inhibited outward whole-cell currents but did not affect inward currents. The respiratory chain complex I inhibitor, rotenone, and complex III inhibitor, antimycin A, were without effect as were kaempferol, an activator of the mitochondrial $Ca^{2+}$ uniporter, and ruthenium red, an inhibitor of the mitochondrial $Ca^{2+}$ uniporter. These results suggest that the inner membrane potential (as regulated by proton ionophores) and the $F_1/F_O$-ATP synthase of mitochondria are important in regulating TRPM7 channels.

Keywords

Antimycin A;CCCP;Mitochondria;Oligomycin;Rotenone;TRPM7

Acknowledgement

Supported by : Korea Science and Engineering Foundation (KOSEF)

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