Automaticity Induced by Ca++ Chelating Agents in Isolated Rabbit Left Atria

Transmembrane potentials were recorded from single cells of isolated rabbit left atria. Action potentials generated by electrical stimulation were markedly depressed or completely abolished by Ca++ chelating agents, EGTA and EDTA (4 and 5 mM), in association with a decrease in the resting membrane potential. Automaticity was initiated. EGTA-induced automaticity was abolished by the addition of 2 mM Ca++. Changes in the membrane potential induced by 5 mM EGTA were reversed by 3 to 5 mM Ca++. Reduction in [Na+]° from 162 mM to 74 or 52 mM delayed the initiation of automaticity, slowed the automatic rate, shortened the duration of automaticity and decreased the action potential amplitude. Magnesium ions (0.1 to 0.2 mM) abolished automaticity induced by EGTA. The resting potential was not significantly changed. Increasing concentrations of Mg++ to 0.5 to 2 mM made preparations unresponsive to electrical stimulation. The addition of Mn++ in concentrations higher than 2mM abolished EGTA-induced atuomaticity in association with increased resting potential. Electrical stimulation generated action potentials, which were not abolished by increasing concentrations of Mn++ but by tetrodotoxin. Atrial contractions abolished by EGTA were temporarily restored by 3 mM Mn++. Automaticity induced by these chelating agents may be associated with increased resting permeability for Na+, permitting membranes to depolarize to a level at which action potentials generate spontaneously. It appears that upon excitation Mg++ decreases the membrane permeability for Na+.