A novel opener of large-conductance Ca2+ -activated K+ (BK) channel reduces ischemic injury in rat cardiac myocytes by activating mitochondrial K(Ca) channel.

Abstract

It has been suggested that a new type of large-conductance Ca(2+)-activated K(+) (BK) channel is distributed in the inner mitochondrial membrane (mitoK(Ca) channel) and that its opening may attenuate ischemic cardiac injury. We examined effects of 12,14-dichlorodehydroabietic acid (diCl-DHAA), a novel BK-channel opener, on rat cardiac myocytes and mitochondria. Application of diCl-DHAA concentration-dependently reduced Ca(2+) overload in isolated mitochondria, activated mitoK(Ca) channels in inside-out patches of mitochondrial membrane, facilitated flavoprotein-oxidization in myocytes, and increased cellular viability under simulated ischemia. In conclusion, diCl-DHAA directly opens mitoK(Ca) channels, prevents Ca(2+) influx into matrix, and reduces ischemic injury in cardiac myocytes.

• Authors: Kazuho Sakamoto, Susumu Ohya, Katsuhiko Muraki, Yuji Imaizumi
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 108 Issue 1 Pg. 135-9 (Sep 2008) ISSN: 1347-8613 [Print] Japan
• PMID: 18758135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 12,14-dichlorodehydroabietic acid
• Abietanes
• Potassium Channels, Calcium-Activated
• Calcium

Topics

• Abietanes (pharmacology)
• Animals
• Calcium (metabolism)
• Cell Survival (drug effects)
• In Vitro Techniques
• Mitochondria, Heart (drug effects, pathology)
• Mitochondrial Membranes (drug effects, metabolism)
• Myocardial Ischemia (pathology, prevention & control)
• Myocytes, Cardiac (drug effects, pathology)
• Oxidation-Reduction
• Patch-Clamp Techniques
• Potassium Channels, Calcium-Activated (agonists)
• Rats