Stretch-activated currents in ventricular myocytes: amplitude and arrhythmogenic effects increase with hypertrophy.

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 (I(SAC)) through non-selective cation channels. I(SAC) followed a linear voltage-dependence, reversed polarity close to 0 mV and was suppressed by 5 microM Gd(3+). During stretch, I(SAC) became steady within 200 ms. I(SAC) did not inactivate and it completely disappeared upon relaxation. Stretch-sensitivity was evaluated from the slope of I(SAC) versus amplitude of stretch. Stretch sensitivity was 75 pA/microm in myocytes from young (3 month), 143 pA/microm in myocytes from old (15 months), and 306 pA/microm in hypertrophied myocytes from old (15 months) spontaneously hypertensive animals. Stretch sensitivity was 262 pA/microm in hypertrophied myocytes from human failing hearts, and it was 143 pA/microm 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, I(SAC) being the current with the largest arrhythmogenic potential. Stretch-sensitivity of I(SAC) 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.