مرکز منطقه ای اطلاع رساني علوم و فناوري - Role of TRPM cation channels on molecular Ca^2+ signaling pathways in heart

Abstract :

The transient receptor potential (TRP) melastatin (TRPM) channel family consist of eight mammalian cation channels within four subgroups and is expressed in almost every tissue, including the heart and vascular systems. All TRPM channels are permeable to Ca^2+ and Na+. The family members are activated by different activators. For example, TRPM2 cation channels can be gated either by ADP-ribose (ADPR) in concert with high (1μM) Ca^2+, or by hydrogen peroxide (H2O2), which provides an experimental model for oxidative stress. The activation of the TRPM2 channel through poly (ADP-Ribose) polymerase (PARP) is also involved in oxidative stress-induced cardiomyocyte death. TRPM4 participates in some features of cardiac arrhythmias. A functional hallmark of TRPM4 is also a dramatic shift of its voltage dependence towards negative, physiologically meaningful potentials. TRPM4 is also functionally expressed in sino-atrial cells and may be a key player in the generation and/or perturbation of heart rhythm. Experimental studies with respect to patch-clamp and Ca^2+ imaging, inhibitor roles of antioxidants are also summarized in the review. In conclusion, we observed that TRPM channels in the current review study have potential to become important novel pharmacological targets for the treatments of human cardiovascular diseases.