Mitochondrial benzodiazepine receptor linked to inner membrane ion channels by nanomolar actions of ligands

Kathleen W. Kinnally, Dmitry B. Zorov, Yuri N. Antonenko, Solomon H. Snyder, Maureen W. Mcenery, Henry Tedeschi

Research output: Contribution to journalArticlepeer-review

Abstract

The mitochondrial benzodiazepine receptor (mBzR) binds a subset of benzodiazepines and isoquinoline carboxamides with nanomolar affinity and consists of the voltage-dependent anion channel, the adenine nucleotide translocator, and an 18-kDa protein. The effect of ligands of the mBzR on two inner mitochondrial membrane channel activities was determined with patch-clamp techniques. The relative inhibitory potencies of the drugs resemble their binding affinities for the mBzR. Ro5-4864 and protoporphyrin IX inhibit activity of the multiple conductance channel (MCC) and the mitochondrial centum-picosiemen (mCtS) channel activities at nanomolar concentrations. PK11195 inhibits mCtS activity at similar levels. Higher concentrations of protoporphyrin IX induce MCC but possibly not mCtS activity. Clonazepam, which has low affinity for mBzR, is at least 500 times less potent at both channel activities. Ro15-1788, which also has a low mBzR affinity, inhibits MCC at very high concentrations (16 μM). The findings indicate an association of these two channel activities with the proteins forming the mBzR complex and are consistent with an interaction of inner and outer membrane channels.

Original languageEnglish (US)
Pages (from-to)1374-1378
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number4
DOIs
StatePublished - Feb 15 1993

Keywords

  • Heart
  • Patch clamp
  • Permeability transition
  • Protoporphyrin
  • Transport

ASJC Scopus subject areas

  • General

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