Functional expression of the TRPM4 cationic current in ventricular cardiomyocytes from spontaneously hypertensive rats

被引:93
作者
Guinamard, Romain [1 ]
Demion, Marie [1 ]
Magaud, Christophe [1 ]
Potreau, Daniel [1 ]
Bois, Patrick [1 ]
机构
[1] Univ Poitiers, CNRS, UMR 6187, Inst Physiol & Biol Cellulaires, F-86022 Poitiers, France
关键词
hypertrophy; cation channel; ventricular function;
D O I
10.1161/01.HYP.0000237864.65019.a5
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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+. Open probability was increased by depolafization and a rise in [Ca2+](i) (dissociation constant = 10 +/- 5.4 mu mol/L) but reduced by 0.5 mmol/L [ATP](i), 10 mu mol/L glibenclamide, or flufenamic acid (IC50=5.5 +/- 1.7 mu mol/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 cafdiomyocytes. 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 [Ca2+] overload of cafdiomyocytes.
引用
收藏
页码:587 / 594
页数:8
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