The mechanism of barium-induced automaticity in ventricular muscle fibers

When 2 mM BaCl2 was applied to dog ventricular muscle fibers that never showed a pacemaker activity under physiological conditions, muscle fibers depolarized to -46 mV and developed spontaneous activity. This spontaneous activity exhibited slow upstroke velocity and prolonged plateau of action potentials. The frequency of the Ba2+-induced automaticity was dependent on external Ca2+ concentrations and increased with a higher external Ca2+ up to 7.2 mM. The automaticity was abolished in Na+-free solution, high K+ (21.6 mM) solution, and the presence of verapamil. Membrane currents after Ba2+ application were shown to decrease in the steady state current and to increase in the slow inward current. The analysis of changes in the steady state current current revealed a decrease in the background K+ current, but no changes or later increase in the time-dependent K+ current after prolonged exposure to Ba2+. From these results, it is concluded that the Ba2+-induced automaticity is brought about by the decrease in the background K+ current, the increase in the slow inward current, and the activation of the time-dependent K+ current.