Resistance of Embryonic Chick Atria to Inhibition of HCN-Channels and Components of the “Ca²⁺-Clock”

Abstract

Despite its medical importance, the cellular mechanisms activity and the contribution of various ion channels of embryonic heart automatism are not yet fully understood. In this study we investigated the effects of specific ion-channel inhibitors on the generation of action potentials in pacemaker cells of the right atrium in chicken embryos (HH36). We used microelectrode technique and evaluated the sensitivity of pacemaker cells to ivabradine (inhibitor of HCN-channels, through which the hyperpolarization-activated current, If), ryanodine (agonist of ryanodine receptors) and SN6 (inhibitor of Na+/Ca2+-exchange). It was found that the right atrium cells have a phase of slow diastolic depolarization. However, these cells were not sensitive to ivabradine (3 μM). We did not register significant changes in the electrophysiological parameters of action potentials.When ryanodine (1 μM) and SN6 (10 μM) were added to the perfusion solution, we observed similar effects: spontaneous rate the generation of action potential increased by 15%. Disturbance of rhythmic activity or disruption of the generation of electrical impulses were not observed in right atrial samples of chicken embryos. The obtained results allow us to conclude that, at this of embryonic development stage, HCN4-channels, ryanodine receptors, and the Na+/Ca2+-exchange are not decisive for maintaining the automatism of the right atrial cells in the chick embryo. We assume that the ion currents flowing through these channels are important in electrophysiology in adult animals, but they have a modulating function in the embryonic myocardium.