title: Increased sodium-calcium exchange current in right ventricular cell hypertrophy induced by simulated high altitude in adult rats.
abstract: Ventricular hypertrophy is associated with an increase in action potential (AP) duration which is potentially arrhythmogenic. The implication of the Na-Ca exchange current (I(Na-Ca)) in the lengthening of the AP is controversial. The role of this current in the increased duration of the low plateau of the AP in hypertrophied adult rat ventricular myocytes by simulated chronic high-altitude exposure ( approximately 4500 m) was evaluated. Electrophysiological experiments were carried out on isolated right ventricular myocytes from exposed and control rats with the perforated patch or the conventional whole-cell technique in current or in voltage clamp condition. With the two techniques, a significant increase of the low plateau duration was observed in hypertrophied myocytes as compared to controls. The low plateau in hypertrophied myocytes was depressed when Na was replaced by Li and was no longer recorded when intracellular Ca was buffered with EGTA. Inward tail currents, evoked either on repolarization to -80 mV following a depolarizing pulse to +10 mV or by interrupted AP technique, were greater in hypertrophied than in control myocytes and were abolished when Na was replaced by Li or when intracellular Ca was buffered with EGTA, indicating an increased Na-Ca exchange activity. The Li-sensitive current-voltage curves, obtained by a voltage clamp ramp protocol with an intracellular calcium buffered solution, were not significantly different in both hypertrophied and control myocytes, suggesting no modification in the density of the Na-Ca exchange protein. This was corroborated by the lack of difference in NCX1 mRNA levels between right ventricles from control and exposed rats. We conclude that increased duration of the low plateau of rat ventricular AP in altitude cardiac hypertrophy may be attributed to an increase of the inward I(Na-Ca). This augmented I(Na-Ca)may result from a modification in the intracellular Ca homeostasis.
authors.affiliation: UMR CNRS 5578, Physiologie des Régulations Energétiques, Cellulaires et Moléculaires, Campus La Doua, Villeurbanne, 69622, France.
authors.forename: L
authors.initials: L
authors.lastname: Espinosa
authors.forename: C
authors.initials: C
authors.lastname: Chouabe
authors.forename: A
authors.initials: A
authors.lastname: Morales
authors.forename: J
authors.initials: J
authors.lastname: Lachuer
authors.forename: B
authors.initials: B
authors.lastname: Georges
authors.forename: M
authors.initials: M
authors.lastname: Fatemi
authors.forename: C
authors.initials: C
authors.lastname: Terrenoire
authors.forename: Y
authors.initials: Y
authors.lastname: Tourneur
authors.forename: R
authors.initials: R
authors.lastname: Bonvallet
mesh_terms: D000200:Action Potentials; D000531:Altitude; D000818:Animals; D004594:Electrophysiology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000502:physiology
chemical_list: D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1