Na-Ca exchange as a regulator in action potentials of neonatal rat ventricles

Transmembrane action potentials were recorded from intact ventricles of young rats, in control media and after exposure to Cd²⁺, a blocker of Na-Ca exchange. Control action potential durations (APD₉₀s) related directly to stimulation rate with an average slope of 0.48 ms/bpm (3 hearts) between 10 and 120 beats/min (bpm). Rate-dependency of APD was abolished by 4 mM Cd²⁺ (p<0.001). It was concluded that the Na-Ca exchange of neonatal myocytes influences the rate-dependency of their action potential durations. The relationship between Na-Ca exchange and APD was simulated using a voltage-clamped single cell model. Results and simulations suggest that: (1) positive rate-dependency of APD promotes internal Cd ²⁺ accumulation via reverse Na-Ca exchange, and (2) the latter may depend on slow Na influx during action potential plateau at high stimulus rates