Regulation of transient receptor potential melastatin 7 (TRPM7) currents by mitochondria

Byung Joo Kim1, Ju-Hong Jeon, Seon Jeong Kim

  • 1Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.

Molecules and Cells
|July 25, 2007
PubMed

Insights

Mitochondria regulate the TRPM7 ion channel. Changes in mitochondrial membrane potential and ATP synthase activity, influenced by proton ionophores and oligomycin, affect TRPM7 channel function.

Area of Science:

  • Cell Biology
  • Biophysics
  • Molecular Physiology

Background:

  • Mitochondria are crucial for cellular energy production.
  • Mitochondria are increasingly recognized for their roles in regulating ion channels and receptors.
  • The transient receptor potential melastatin 7 (TRPM7) is a bifunctional enzyme with both ion channel and kinase activity.

Purpose of the Study:

  • To investigate the role of mitochondria in regulating the TRPM7 ion channel.
  • To elucidate how mitochondrial function impacts TRPM7 channel activity.

Main Methods:

  • Whole-cell patch-clamp electrophysiology was used to record TRPM7 currents.
  • Mitochondrial function was manipulated using proton ionophores (CCCP) and inhibitors of ATP synthase (oligomycin).
  • Specific inhibitors of respiratory chain complexes (rotenone, antimycin A) and mitochondrial calcium uniporter (kaempferol, ruthenium red) were employed.

Main Results:

  • Proton ionophores (CCCP) altered TRPM7 currents in a MgATP-dependent manner, decreasing outward currents and increasing inward currents without MgATP, but increasing both with MgATP.
  • Oligomycin inhibited outward TRPM7 currents, suggesting a role for ATP synthase.
  • Inhibitors of respiratory chain complexes I and III, and mitochondrial calcium uniporter modulators, did not significantly affect TRPM7 currents.

Conclusions:

  • Mitochondrial inner membrane potential, modulated by proton ionophores, is a key regulator of TRPM7 channel activity.
  • The F1/FO-ATP synthase is involved in regulating outward TRPM7 currents.
  • Mitochondria represent a significant regulatory influence on TRPM7 channel function.

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