New aspects for the treatment of cardiac diseases based on the diversity of functional controls on cardiac muscles: mitochondrial ion channels and cardioprotection.

Abstract

Mitochondrial ATP-sensitive K(+) (mitoK(ATP)) and Ca(2+)-activated K(+) (mitoK(Ca)) channels exist in cardiac myocytes, and they play key roles in cardioprotection. We have recently reported that K(+) influx through mitoK(ATP) or mitoK(Ca) channels occurs independently of each other and confers cardioprotection in a similar manner. Activation of mitoK(ATP) channel is augmented by protein kinase C (PKC), whereas mitoK(Ca) channel is activated by protein kinase A (PKA). However, phosphatidylinositol 3-kinase (PI3-K) is linked to neither mitoK(ATP) nor mitoK(Ca) channels. We have demonstrated that bioactive substances modulate the opening of mitoK(ATP) channels via a PKC-dependent pathway or opening of mitoK(Ca) channels via a PKA-dependent pathway and thereby protecting the heart from ischemia/reperfusion injury. Several endogenous substances such as adenosine and bradykinin can reduce infarct size by activation of mitoK(ATP) channels in a PKC-dependent manner. Adrenomedullin, a potent vasodilator peptide, potentiates the opening of mitoK(Ca) channels by PKA activation. Treatment with adrenomedullin prior to ischemia results in the reduction of infarct size via a PKA-mediated activation of mitoK(Ca) channels. Thus, some endogenous substances confer cardioprotection via PKA- or PKC-mediated activation of mitoK(ATP) or mitoK(Ca) channels.

• Authors: Hirofumi Nishida, Toshiaki Sato, Takehiko Ogura, Haruaki Nakaya
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 109 Issue 3 Pg. 341-7 (Mar 2009) ISSN: 1347-8613 [Print] Japan
• PMID: 19270424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Potassium Channels
• Potassium Channels, Calcium-Activated
• mitochondrial K(ATP) channel
• Adrenomedullin
• Phosphatidylinositol 3-Kinases
• Cyclic AMP-Dependent Protein Kinases
• Protein Kinase C

Topics

• Adrenomedullin (metabolism)
• Animals
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Humans
• Mitochondria, Heart (metabolism)
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Myocytes, Cardiac (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Potassium Channels (metabolism)
• Potassium Channels, Calcium-Activated (metabolism)
• Protein Kinase C (metabolism)