Résumé
Cardiac pacemaking involves several ion channels, which are subtly regulated by autonomic nervous system. The hyperpolarization-activated cyclic nucleotide gated channel, particularly HCN4 subunit, is considered as a major actor for sino-atrial node automaticity. Moreover due to its directly regulation by cAMP, HCN4 channels have been proposed as one of the main responsible for the increase of heart rate after sympathetic stimulation. However its relative importance remains highly controversial.
To investigate the role of HCN channel in cardiac automaticity and sympathetic regulation, we used telemetric ECG recording techniques in two specific mouse strains: one with a conditional complete suppression of HCN4 conductance (HCN4-AYA) and the second with a loss of cAMP-mediated modulation of HCN4 (HCN4-CNBD).
Our results show that in the two strains heart rate is reduced by the same percentage with respect to the wild type. During pharmacological sympathetic stimulation the maximal heart rate was lower in the two transgenic strains than in wild type, but the relative extent of heart rate remains the same for all mice.
Our data confirm the importance of HCN4 for cardiac pacemaking both at rest and during sympathetic stimulation, and that the presence of cAMP is essential for HCN4 function. Moreover, our results seem to indicate that this channel is not indispensible for heart rate autonomic regulation.