Action potential responses to changes in stimulation frequency and isoproterenol in rat ventricular myocytes

Current understanding of ventricular action potential adaptation to physiological stress is generally based on protocols using non-physiological rates and conditions isolating rate effects from escalating adrenergic stimulation. To permit refined understanding, ventricular action potentials were assessed across physiological pacing frequencies in the presence and absence of adrenergic stimuli. Isolated and combined effects were analyzed to assess their ability to replicate in-vivo responses.

Steady-state action potentials from ventricular myocytes isolated from male Wistar rats (3 months; N = 8 animals) were recorded at 37°C with steady-state pacing at 1, 2, 4, 6, 8 and 10 Hz using whole-cell patch-clamp. Action potential repolarization to 25, 50, 75, 90 and 100% of full repolarization (APD_25-100 ) was compared before and after 5 nM, 100 nM and 1 µM isoproterenol doses.

A Repeated measures ANOVA found APD_50-90  shortened with 5 nM isoproterenol infusion by 6-25% (but comparable across doses) (p ≤ 0.03). Pacing frequencies emulating a normal rat heart rate (6 Hz) prolonged APD₅₀ 23% compared with 1 Hz pacing. Frequencies emulating exercise or stress (10 Hz) shortened APD₉₀ (29%).

These results demonstrate modest action potential shortening in response to adrenergic stimulation and elevations in pacing beyond physiological resting rates. Our findings indicate changes in action potential plateau and late repolarization predominantly underlie simulated exercise responses in the rat heart. This work provides novel action potential reference data and will help model cardiac responses to physiological stimuli in the rat heart via computational techniques.