INTERACTIVE EFFECTS OF VARIATIONS IN [NA](0) AND [CA](0) ON RAT ATRIAL SPONTANEOUS FREQUENCY

The effects of varying the extracellular concentrations of Na and Ca ( [Na]0 and [Ca]0) on both, the spontaneous beating and the negative chr onotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +/- 4 b eats/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by. lowering [Na]0 to 78 mM (LNa), 23 /- 2% by lowering simultaneously [Na]0 to 78 mM and [Ca]0 to 0.675 mM (LNa + LCa) and 31 +/- 5% by lowering [Na]0 to 78 mM plus increasing [ Ca]0 to 3.6 mM (LNa + HCa). At normal [Na]0, decrease (0.675 mM) or in crease (3.6 mM) of [Ca]0 did not modify BF; a reduction of ten times ( 0.135 mM of normal [Ca]0 was effective to reduce BF by 40 +/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent brady cardia induced by verapamil was potentiated by LNa, LCa and HCa. Indep endent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]0 needed to reduce BF by 30% (IC30) with the following order of inhibitory potency LNa > LCa > HCa > N, resulting LNa + HCa similar to LNa. The [verapamil]0 that arrested atrial beatin g (AC) was also potentiated with the order LNa = LNa + LCa = LNa + HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous bea ting is more dependent on [Na]0 than on [Ca]0 in a range of +/- 50% of their normal concentrations. Also the enhancement of verapamil effect s on atrial beating was more pronounced at LNa than at LCa. It is poss ible that both, Na and Ca may be determining two different ionic perme abilities or currents playing a role in supporting the resting potenti al or i(si) on which rat atrial rate depends.