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Updated: Aug 22, 2025

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
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External Hemin as an Inhibitor of Mitochondrial Large-Conductance Calcium-Activated Potassium Channel Activity

Agnieszka Walewska1, Adam Szewczyk1, Piotr Koprowski1

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

International Journal of Molecular Sciences
|November 11, 2022
PubMed

Insights

Hemin inhibits the mitochondrial large-conductance calcium-activated potassium channel (mitoBKCa) by binding to a newly discovered site on the intermembrane space side. This finding reveals a novel regulatory mechanism for mitoBKCa channel activity.

Area of Science:

  • Mitochondrial physiology
  • Ion channel function
  • Biochemistry

Background:

  • The mitochondrial large-conductance calcium-activated potassium channel (mitoBKCa) is vital for cytoprotection.
  • Heme and hemin are known inhibitors that bind to the mitochondrial matrix side of mitoBKCa.

Purpose of the Study:

  • To investigate the effect of hemin on mitoBKCa channel activity when applied to the intermembrane space.
  • To identify potential new binding sites for heme/hemin on the mitoBKCa channel.

Main Methods:

  • Utilized patch-clamp technique in the outside-out configuration to record mitoBKCa channel activity.
  • Applied hemin to the intermembrane-space side of the mitoBKCa channel.

Main Results:

  • Hemin applied to the intermembrane space inhibited mitoBKCa channel activity.
  • The observed inhibition was specific and not due to interaction with the inner mitochondrial membrane.
  • Data suggest a novel heme/hemin binding site on the mitochondrial intermembrane space side of mitoBKCa.

Conclusions:

  • A new potential heme/hemin binding site exists on the intermembrane space side of the mitoBKCa channel.
  • This site offers a novel regulatory pathway for mitoBKCa channel function.
  • Further research into this binding site could reveal new therapeutic targets.

Keywords:
BKCa channelheme-binding siteheminhydrogen sulfidemitochondria

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