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Functional Expression of the TRPM4 Cationic Current in Ventricular Cardiomyocytes From Spontaneously Hypertensive Rats

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Guinamard, Romain | Demion, Marie | Magaud, Christophe | Potreau, Daniel | Bois, Patrick

Edité par CCSD ; American Heart Association -

International audience. Cardiac hypertrophy is associated with electrophysiological modifications, including modification of action potential shape that can give rise to arrhythmias. We report here a higher detection of a calcium-activated nonselective cation current in cardiomyocytes of spontaneously hypertensive rats (SHRs), a model of hypertension and heart hypertrophy when compared with Wistar-Kyoto (WKY) rat, its normotensive equivalent. Freshly isolated cells from the left ventricles of 3- to 6-month-old WKY rats or SHRs were used for patch-clamp recordings. In inside-out patches, the channel presented a linear conductance of 25±0.5 pS, did not discriminate Na + over K + , and was not permeable to Ca 2+ . Open probability was increased by depolarization and a rise in [Ca 2+ ] i (dissociation constant=10±5.4 μmol/L) but reduced by 0.5 mmol/L [ATP] i , 10 μmol/L glibenclamide, or flufenamic acid (IC 50 =5.5±1.7 μmol/L). Thus, it owns the fingerprint of the TRPM4 current. Although rarely detected in WKY cardiomyocytes, the current was present in >50% of patches from SHR cardiomyocytes. Moreover, by performing RT-PCR from ventricular samples, we observed that TRPM4 mRNA detection was higher in SHRs than in WKY rats. We propose that a TRPM4 current is expressed in ventricular cardiomyocytes from SHRs. According to its properties, this channel may contribute to the transient inward current implicated in delayed-after-depolarizations observed during [Ca 2+ ] overload of cardiomyocytes.

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