Supraventricular pacemaker activity in the canine heart: contributions from HCN channels in control conditions and in a model of heart failure.

An interesting and clearly presented paper from the Nattel Research Group [1] in this volume of Cardiovascular Research provides new evidence for the expression of three isoforms of hyperpolarization-activated cyclic nucleotidegated ion channels (HCN) in the sinoatrial node and atria of the adult canine heart. These measurements have been made under control conditions, and in the setting of a model of congestive heart failure–tachycardia-induced sinus node dysfunction. A major premise of this study is that although it is wellknown that transmembrane ionic currents generated by HCN ion channels contribute to pacemaker activity, there appear to be significant species differences, and little information on this topic is available for the canine heart. The adult canine is a useful model for making control measurements and then studying selected pathophysiological paradigms which may be relevant to human clinical cardiac electrophysiology and to heart failure [2–5]. The immunohistochemical, molecular, and protein biochemical analyses in this paper show that in this canine model, myocytes from within the sinoatrial node region express the isoforms of this current which have been denoted HCN1, HCN2, and HCN4, with HCN2 and HCN4 predominating. Under control conditions, somewhat similar patters of results are obtained from the right atrium. Interestingly, however, in preparations from animals in which congestive heart failure was induced by overdrive pacing, the pattern of HCN expression in the sinoatrial node showed a decrease in HCN2 and HCN4; while in the right