Effects of species-dependent differences in action potential shape in setting β-adrenergic-stimulation induced current

In canine (D) and human, but not guinea pig (GP), ventricular myocytes, a spike-and-dome profile (SaD), supported by Ito, characterizes ventricular repolarization. β-adrenergic stimulation (by isoprenaline, ISO) shortens action potential (AP) duration (APD) in D (and human) myocytes, but prolongs it in GP ones. Aim: The aim of this work is to clarify whether SaD is the main factor determining the direction of APD response to β-adrenergic stimulation. Methods: AP-clamp with D epicardial, D endocardial, and GP waveforms was applied at different diastolic intervals (DI) to measure ISO-induced current (I_iso) in GP myocytes. Dynamic Clamp was used to test the effect of Ito introduction, and of the resulting SaD, on ISO modulation of GP repolarization. Results: In AP-clamp at DI 1750 ms, I_iso was more inward with both D and GP waveforms. In Dynamic-Clamp, SaD introduction failed to change the direction of ISO-induced APD changes in GP myocytes. Conclusions: SaD profile alone may not account for differences between D and GP in terms of APD response to β-adrenergic-stimulation. Further differences of AP profile and/or diverse contributions of Ca²⁺ and K⁺ currents between the two species may be involved.