Ouabain actions on the spontaneous activity and ionic currents in rabbit sino-atrial node cells

Abstract

1. 1. The effects of ouabain on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using the two-microelectrode technique. 2. 2. Cumulative administrations of ouabain (10 −8 to 10 −6M) caused a negative chronotropic effect in a concentration-dependent manner. The effect was not modified by atropine (10 −7 M). At 10 −6 M, ouabain prolonged the duration of action potentials, but other parameters were unaffected to any significant extent. Ouabain elicited an arrhythmia, and increasing concentrations increased the incidence of arrhythmia (75% at 3 × 10 −7M). 3. 3. Pretreatment with clonidine (10 −6 M), a selective agonist of presynaptic α 2-adrenoceptors, completely blocked the development of arrhythmia induced by ouabain (3 × 10 −7M). Prazosin (10 −6 M), an α 1 antagonist, had similar effects, and yohimbine (10 −6 to 10 −5 M), an α 2 antagonist, did not affect the arrhythmias. 4. 4. Ouabain (10 −8 to 10 −6 M) inhibited the slow inward and the time-dependent outward currents, but enhanced the hyperpolarization-activated inward current, in a concentration-dependent manner. The time course of inactivation phase for I si was composed of two (fast and slow) components. Ouabain decreased the fast component and increased the slow component. The voltage of half-maximum activation for the outward current was not affected. Ouabain elicited a transient inward current on the repolarizing step, and also on the depolarizing step. 5. 5. These results indicate that ouabain inhibits the slow inward and time-dependent outward currents, but elicits arrhythmias due to the induction of cellular calcium overload, which are modulated by α-adrenoceptors.