Roles of TRP channels in the development of cardiac hypertrophy.
Cardiac hypertrophy is induced by various stresses such as hypertension and myocardial infarction. It is believed that hypertrophy is adaptive in the early phase but becomes maladaptive in the late phase. Cardiac hypertrophy develops heart failure when the heart is exposed persistently to the stresses. The increase in intracellular Ca(2+) ([Ca(2+)](i)) plays an important role in the development of hypertrophy. It is generally thought that the increase in [Ca(2+)](i) for hypertrophy occurs via G(q)-stimulated production of inositol-1,4,5-trisphosphate (IP(3)) and IP(3)-mediated release of Ca(2+) from intracellular store. However, several groups recently reported that canonical transient receptor potential (TRPC) channels are responsible for the increase in [Ca(2+)](i). Among them, three TRPC subtypes (TRPC3/TRPC6/TRPC7) are activated by another G(q)-mediated second messenger, diacylglycerol. Although several groups independently demonstrated that TRPC channels mediate receptor-stimulated and pressure overload-induced hypertrophy, there is discrepancy of which subtypes of TRPC channels predominantly mediate hypertrophy. However, there is consensus that TRPC-mediated Ca(2+) influx is essential for hypertrophy. As TRPC channels participate in pathological hypertrophy, but not physiological contraction and the relaxation cycle, TPRC channels are a new target for the treatment of hypertrophy.
Nishida
Motohiro
M
Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Kurose
Hitoshi
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D050051:Transient Receptor Potential Channels / Q000502:physiology*
D050051:Transient Receptor Potential Channels; D002118:Calcium