A Novel Opener of Large-Conductance Ca2+-Activated K+ (BK) Channel Reduces Ischemic Injury in Rat Cardiac Myocytes by Activating Mitochondrial KCa Channel

[摘要] References(15)Cited-By(13)It has been suggested that a new type of large-conductance Ca2+-activated K+ (BK) channel is distributed in the inner mitochondrial membrane (mitoKCa 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 Ca2+ overload in isolated mitochondria, activated mitoKCa 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 mitoKCa channels, prevents Ca2+ influx into matrix, and reduces ischemic injury in cardiac myocytes.

[学科分类] 药学

[关键词] mitochondria;large-conductance Ca2+-activated K+ (BK) channel;cardiac ischemia