Role of membrane potential in Ba2+ induced automatieity in guinea pig cardiac myocytes

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Abstract
Study objective – The aim was to study in isolated myocardial cells the role of membrane potential in barium induced spontaneous activity and the ionic mechanism of the underlying pacemaker current. Design – The membrane potential and resistance of single myocytes were studied at different voltage levels by means of current and voltage clamp steps in the absence and presence of barium (Ba). Experimental material – The membrane potentials and currents of single guinea pig ventricular myocytes were recorded by means of an intracellular microelectrode through which current could also be passed. Measurements and main results – In the presence of Ba (0.1-0.2 mM), stepwise depolarisations induced a transient overshoot and initiated action potentials followed by an undershoot, diastolic de-polarisation and spontaneous discharge. During progressive depolarisations, membrane resistance (Rm) increased, decreased transiently at the end of the action potential, and reincreased during diastole. Stepwise repolarisations had opposite effects. Hyperpolarisations reversed diastolic depolarisa-tion and could unmask oscillatory potentials (Vos). Voltage clamp steps to +20 mV were followed by outward tail currents during which Rm increased. Larger or longer depolarisations were followed by larger outward tail currents at resting potential level. The outward tail current reversed at potentials negative to EK. Conclusions – In the presence of Ba, applied depolarisation facilitates the induction of spontaneous activity through an interplay between voltage dependent and time dependent Ba block and unblock of gK1, voltage dependent increase in Rm, increased potassium driving force, and negative shift in the slow inward current threshold and sometimes Vos. The pacemaker potential underlying spontaneous activity is due to the slow re-establishment of Ba block of IK1 during diastole.

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