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Pharmacological Characterization of a Recombinant Mitochondrial ROMK2 Potassium Channel Expressed in Bacteria and

Milena Krajewska1,2, Adam Szewczyk1, Bogusz Kulawiak1

  • 1Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland.

Membranes
|March 29, 2023
PubMed

Insights

The ROMK2 potassium channel, a potential part of the mitochondrial ATP-regulated potassium channel (mitoKATP), is modulated by known mitoKATP drugs. This suggests ROMK2 may form the core of the mitoKATP channel.

Area of Science:

  • Mitochondrial physiology
  • Ion channel biophysics
  • Molecular biology

Background:

  • Mitochondrial potassium channels regulate cell survival and death.
  • The ATP-regulated potassium channel (mitoKATP) is a key regulator.
  • The ROMK2 potassium channel is a candidate component of mitoKATP.

Purpose of the Study:

  • To investigate the pharmacological modulation of ROMK2 channel activity.
  • To determine if ROMK2 is functionally similar to mitoKATP.
  • To explore the role of ROMK2 in the context of mitoKATP function.

Main Methods:

  • Expressing ROMK2 in *Escherichia coli*.
  • Solubilizing ROMK2 in polymer nanodiscs.
  • Incorporating ROMK2 into planar lipid bilayers for electrophysiological recordings.

Main Results:

  • ROMK2 channel activity was activated by diazoxide, a known mitoKATP opener.
  • ROMK2 was inhibited by ATP/Mg2+, 5-hydroxydecanoic acid, and glibenclamide, classic mitoKATP inhibitors.
  • These modulations occurred independently of accessory proteins.

Conclusions:

  • The ROMK2 potassium channel protein may serve as the pore-forming subunit of the mitoKATP channel.
  • Pharmacological responses of ROMK2 mimic those of the native mitoKATP channel.
  • The findings support ROMK2's role in mitochondrial potassium transport and cell death regulation.
Keywords:
ROMK2mitoKATP channelplanar lipid bilayerpolymer nanodiscspotassium channel modulators

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