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.