The L type calcium current in single hypertrophied cardiomyocytes isolated from the right ventricle of ferret heart

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Abstract
Objective: The aim was to study L type calcium current alterations in relation to the action potential lengthening induced by hypertrophy in isolated cardiomyocytes from the right ventricle of ferret. Methods: Chronic pulmonary artery constriction was established in adult male ferrets under anaesthesia. Sham operated animals were used as controls. Four to six weeks later the heart was excised and treated with a mixed collagenase-elastase solution to isolate the right ventricular myocytes. The calcium current was investigated in control and hypertrophied cells with the whole cell configuration of the patch clamp technique. The validity of the model was tested by analysis of the structural and passive electrical characteristics of the cells, which were enzymatically isolated from right ventricles previously overloaded (4 to 6 weeks) by clipping the pulmonary artery. Results: Isolated cells from right ventricles submitted to a chronic pressure overload had well preserved cellular integrity suggesting the absence of myocardial failure. This compensated form of hypertrophy was characterised by a dilated transverse tubular system, which could explain the increased membrane capacity. Such cells developed a prolonged action potential with a less pronounced fast repolarisation phase inducing a higher plateau phase. When studied in physiological Tyrode solution the density and kinetics of the L type calcium current were not apparently modified, but a significant decrease in density was unmasked when sodium and potassium currents were suppressed by external and internal substitution of sodium and potassium by tetraethyl ammonium. Conclusions: The decrease in L type calcium current cannot be involved in the lengthening of action potential observed on hypertrophied myocytes, but it could account for the depressed contractile activity. A noticeable decrease of the transient outward current is suggested to explain the action potential alterations.

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