0150 : Endurance training induced functional TRPM4 channel expression in mouse left ventricle

AimTransient Receptor Potential (TRP) channels, in particular the TRPC subclass, have been shown as pathological cardiac hypertrophy (CH) regulators probably via the Cn-NFAT pathway activation. By contrast, the physiological CH depends on the IGF-1-PI3K-Akt pathway activation. The TRPM4 channel is a Ca2+-activated channel weakly expressed at the ventricular level while it seems to be a negative regulator of TRPC channel and could be also re-expressed in ventricle during pathological CH. Our purpose was to determine whether TRPM4 channel could be involved in physiological CH and what are the consequences on Ca2+ homeostasis.Methods and ResultsTo induce physiological CH, mice were assigned to sedentary or treadmill running (TR). Echocardiograms demonstrated that mice displayed morpho-functional cardiac adaptations associated with an increase of P-Akt/Akt protein ratio validating physiological CH in TR mice. TRPM4 channel mRNA was increased in the ventricle of trained mice, associated with protein detection. Using the patch-clamp technique, we unmasked a Ca2+-activated non-selective cationic current, which shares the eletrophysiological properties of those recorded for the TRPM4 channel. We use of a selective TRPM4 inhibitor, 9-Phenanthrol, to blunt TRPM4 channel activity during the excitation-contraction coupling (ECC) recording under Isoproterenol stimulation, a β agonist. Treated cardiomyocytes displayed a diastolic [Ca2+] and maximal Ca2+ amplitude decreased, underlying TRPM4 channel involvement in ECC.ConclusionThis study provides the first evidence of functional TRPM4 channel re-expression during physiological CH and its potential role in Ca2+ homeostasis