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

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. Cumulative administrations of ouabain (10(-8) to 10(-6) M) 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 x 10(-7) M). 3. Pretreatment with clonidine (10(-6) M), a selective agonist of presynaptic alpha 2-adrenoceptors, completely blocked the development of arrhythmia induced by ouabain (3 x 10(-7) M). Prazosin (10(-6) M), an alpha 1 antagonist, had similar effects, and yohimbine (10(-6) to 10(-5) M), an alpha 2 antagonist, did not affect the arrhythmias. 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 Isi 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.(ABSTRACT TRUNCATED AT 250 WORDS)