KB-R7943 Inhibits the Mitochondrial Ca2+ Uniporter but Not Na+-Ca2+ Exchanger in Cardiomyocyte-Derived H9c2 Cells

Biol Pharm Bull. 2020 Dec 1;43(12):1993-1996. doi: 10.1248/bpb.b20-00747. Epub 2020 Oct 6.

Abstract

The effect of KB-R7943, an inhibitor of the plasmalemmal Na+-Ca2+ exchanger, on mitochondrial Ca2+ transporters was examined with membrane-permeabilized cardiomyocyte-derived H9c2 cells expressing the fluorescent Ca2+ indicator, yellow cameleon 3.1, in the mitochondria. KB-R7943, as well as ruthenium red, inhibited the rise in mitochondrial Ca2+ on increasing the extramitochondrial Ca2+ concentration from 0 nM to 300 nM. CGP-37157, but not KB-R7943, inhibited the decline in mitochondrial Ca2+on return to Ca2+ free extramitochondrial solution. These results indicated that KB-R7943 has inhibitory effects on the mitochondrial Ca2+ uniporter, but not on the mitochondrial Na+-Ca2+ exchanger.

Keywords: Ca2+ imaging; Ca2+ uniporter; KB-R7943; Na+–Ca2+ exchanger; cardiomyocyte; mitochondria.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / drug effects*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Clonazepam / analogs & derivatives
  • Clonazepam / pharmacology
  • Mitochondria / metabolism
  • Myocytes, Cardiac / drug effects
  • Rats
  • Sodium / metabolism
  • Sodium-Calcium Exchanger / drug effects*
  • Sodium-Calcium Exchanger / metabolism
  • Thiazepines / pharmacology
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology

Substances

  • 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
  • Calcium Channels
  • Sodium-Calcium Exchanger
  • Thiazepines
  • mitochondrial calcium uniporter
  • Clonazepam
  • CGP 37157
  • Sodium
  • Thiourea
  • Calcium