title: Functional expression of the TRPM4 cationic current in ventricular cardiomyocytes from spontaneously hypertensive rats.
abstract: 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 micromol/L) but reduced by 0.5 mmol/L [ATP](i), 10 micromol/L glibenclamide, or flufenamic acid (IC(50)=5.5+/-1.7 micromol/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.
authors.affiliation: Institut de Physiologie et Biologie Cellulaires, Centre National de la Recherche Scientifique Unité Mixte de Recherche, Université de Poitiers, Poitiers, France. romain.guinamard@univ-poitiers.fr
authors.forename: Romain
authors.initials: R
authors.lastname: Guinamard
authors.forename: Marie
authors.initials: M
authors.lastname: Demion
authors.forename: Christophe
authors.initials: C
authors.lastname: Magaud
authors.forename: Daniel
authors.initials: D
authors.lastname: Potreau
authors.forename: Patrick
authors.initials: P
authors.lastname: Bois
mesh_terms: D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D016276:Ventricular Function
chemical_list: D012333:RNA, Messenger; D050053:TRPM Cation Channels; C500239:TRPM4 protein, rat