Membrane currents linked to barium-induced pacemaker activity in the bullfrog atrium.

Ionic mechanisms underlying Ba2+-induced automaticity in the bullfrog atrial muscle were studied by performing current and voltage clamp experiments using the double sucrose-gap technique. The application of Ba2+ of more than 0.01 mM induced membrane depolarization, and its amplitude became larger with increasing [Ba2+]o. Pacemaker activity was initiated above 0.3 mM Ba2+. Voltage clamp experiments revealed a marked decrease in the membrane conductance during hyperpolarizing steps, suggesting a depression of anomalous rectifier (Ikl). The time course of the outward current tail was fitted with a sum of fast (tau not equal to 0.8 s) and slow (tau not equal to 4-5 s) exponential components. The slow component (Ia) was markedly depressed by Ba2+, but the fast component (Ixs) remained. There was no significant change in the slow inward current (Isi). The hyperpolarization-activated current had an activation threshold of about -90 mV and was depressed by Ba2+ at concentrations higher than 1 mM. The pacemaker activity was suppressed by depleting either Na+ or Ca2+ in the bath solutions. The activation of the Isi might be responsible for both the later phase of the pacemaker depolarization and the rapid rising of the spontaneous action potential during low-voltage oscillation; the sodium current might take a similar role in the high-voltage oscillation. The Ixs may play the major role in generating the diastolic depolarization. The suppression of the Ikl and Ia by Ba2+ may provide a low background K conductance, which is essential for the initiation of the pacemaker activity.