Regulation of transient receptor potential melastatin 7 (TRPM7) currents by mitochondria.
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 F1/FO-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 Ca2+ uniporter, and ruthenium red, an inhibitor of the mitochondrial Ca2+ uniporter. These results suggest that the inner membrane potential (as regulated by proton ionophores) and the F1/FO-ATP synthase of mitochondria are important in regulating TRPM7 channels.
Kim
Byung Joo
BJ
Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Jeon
Ju-Hong
JH
Kim
Seon Jeong
SJ
So
Insuk
I
Kim
Ki Whan
KW
D000255:Adenosine Triphosphate / Q000032:analysis / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D050053:TRPM Cation Channels / Q000378:metabolism* / Q000502:physiology*
D015220:Calcium Channels; D007476:Ionophores; D009840:Oligomycins; D050053:TRPM Cation Channels; C034703:mitochondrial calcium uniporter; D012402:Rotenone; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000968:Antimycin A; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D006180:Proton-Translocating ATPases