Pharmacological discrimination of plasmalemmal and mitochondrial sodium-calcium exchanger in cardiomyocyte-derived H9c2 cells.
We examined the effects of SEA0400 and CGP-37157 on the plasmalemmal Na(+)-Ca(2+) exchanger (NCX) and mitochondrial NCX using H9c2 cardiomyocytes loaded with Ca(2+)-sensitive fluorescent probes. The plasmalemmal NCX activity, which was measured as the increase in cytoplasmic Ca(2+) concentration after application of low Na(+) extracellular solution, was inhibited by SEA0400 but not by CGP-37157. The mitochondrial NCX activity, which was measured in permeabilized H9c2 cells as the decrease in mitochondrial Ca(2+) concentration after application of Ca(2+)-free extramitochondrial solution, was inhibited by CGP-37157 but not by SEA0400. These results indicate that SEA0400 and CGP-37157 act as selective inhibitors towards plasmalemmal and mitochondrial NCX, respectively, and provide pharmacological evidence that the plasmalemmal and mitochondrial NCX are distinct molecular entities.
Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences.
Iyuki
I
Namekata
Shogo
S
Hamaguchi
Hikaru
H
Tanaka
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010647:Phenyl Ethers / Q000494:pharmacology*; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology*
D000814:Aniline Compounds; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; C079032:CGP 37157; D002118:Calcium