© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Stretch-activated currents in ventricular myocytes: amplitude and arrhythmogenic effects increase with hypertrophy
Department of Physiology, Martin Luther University, Magdeburgerstrasse 6, D-06097 Halle, Germany
* Corresponding author. Tel.: +49-345-557-1886; fax: +49-345-557-4019 gerrit.isenberg{at}medizin.uni-halle.de
Background: Mechanical dilation of the human ventricle is known to induce arrhythmias, the underlying ionic mechanisms, however, remain to be clarified. Methods: Ventricular myocytes isolated from human, guinea-pig or rat hearts were stretched between the patch electrode and a glass stylus. Results: Local stretch prolonged the action potential, depolarized the resting membrane and caused extra systoles. Under voltage-clamp conditions, stretch activated several ionic current components. The most prominent current was a stretch activated current (ISAC) through non-selective cation channels. ISAC followed a linear voltage-dependence, reversed polarity close to 0 mV and was suppressed by 5 µM Gd3+. During stretch, ISAC became steady within 200 ms. ISAC did not inactivate and it completely disappeared upon relaxation. Stretch-sensitivity was evaluated from the slope of ISAC versus amplitude of stretch. Stretch sensitivity was 75 pA/µm in myocytes from young (3 month), 143 pA/µm in myocytes from old (15 months), and 306 pA/µm in hypertrophied myocytes from old (15 months) spontaneously hypertensive animals. Stretch sensitivity was 262 pA/µm in hypertrophied myocytes from human failing hearts, and it was 143 pA/µm in guinea-pig ventricular myocytes. Conclusions: Local stretch of adult single ventricular myocytes can induce arrhythmias that resemble surface-recordings from whole hearts. Stretch modulates multiple current components, ISAC being the current with the largest arrhythmogenic potential. Stretch-sensitivity of ISAC is higher in hypertrophied than in control myocytes as can be expected from the observation that hypertrophy and failure increase the risk of stretch-induced arrhythmias.
KEYWORDS Arrhythmia (mechanisms); Hypertrophy; Ion channels; Membrane currents; Membrane potential; Stretch/m–e coupling; Ventricular arrhythmias
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