Novel Strategy for Cardioprotection by TRPM4 Inhibitor
July 31, 2013
Researchers in the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences have revealed that the development of myocardial infarction is reduced by 9-phenanthrol, transient receptor potential cation channel subfamily M member 4 (TRPM4) inhibitor. In addition, the effect of 9-phenanthrol was not affected when KATP channels were inactivated.
The findings were published online on July 25, 2013 in the journal PLoS One.
As prevention and treatment for myocardial infarction, drugs such as adenosine are under clinical trials now. The action mechanism of adenosine is to activate KATP (ATP-sensitive potassium) channels in mitochondria of cardiac cells.
TRPM4 is functionally expressed in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases.
K. Takahashi and his colleagues have examined the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4 in rat hearts. In rat hearts pretreated with 9-phenanthrol before subjected to global ischemia, contractile function recovered dramatically, and the size of infarcted area decreased to less than 1/4 compared to controls. In addition, the cardioprotective effects of 9-phenanthrol were not completely blocked by 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel).
In patients with heart failure or diabetes mellitus, mitochondria functions are decreased. Therefore, TRPM4 inhibitors have more advantages for use in a prevention and treatment drug of myocardial infarction in patients with comorbidities than a blocker of the ATP-sensitive potassium channel in mitochondria.
The findings suggest that TRPM4 may serve as an effective pharmacological target for cardioprotective treatment strategies and could lead the development of a novel drug based on a new mechanism.
Mototaka Senda, Ph.D.
Intellectual Property Office, Organization for Research Promotion and Collaboration, Okayama University
Fremont, California USA
Ken Takahashi, Ph.D.
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan