Evidence from Impedance Spectroscopy that Elevated Dopamine Reduces Mitochondrial Membrane Potential

Abstract

Background: Recent studies suggest that elevated dopamine concentrations reduce mitochondrial membrane potential, potentially contributing to neurological or other disorders. Changes in average membrane potential of suspended cells or organelles can be monitored in real time by measuring impedance of the suspension as a labelfree assay. Methods/Results: Here we report on measurements of frequency- and time-dependent electrical impedance of mitochondrial suspensions in the presence of various substrates, including dopamine. We find that, during succinateinduced state-2 respiration, addition of either trifluoromethoxy carbonylcyanide phenylhydrazone (FCCP), a known mitochondrial uncoupler (depolarizer), or dopamine at high concentrations cause similar increases in impedance, consistent with a drop in mitochondrial membrane potential. Conclusion: Our results provide further evidence that dopamine reduces mitochondrial membrane potential, albeit less severely than FCCP, possibly by generating free radicals that partially perforate the mitochondrial inner membrane and/or reduce activity of respiratory complexes. These results suggest that prolonged excess dopamine can impair ATP production, with possible implications in some neurological disorders and suggesting the need for care in the use of dopamine to treat Parkinson’s disease or heart failure.