The hyperpolarisation-activated current,I f, is not required for pacemaking in single cells from the rabbit atrioventricular node

Abstract

The atrioventricular node (AVN) is vital for cardiac function. One of its properties is that it can act as a pacemaker for the ventricles if the sinoatrial node fails. This study investigates the role of the hyperpolarisation-activated inward current (I(f)) in generating pacemaker activity in morphologically normal single cells isolated from the rabbit AVN. Whole-cell patch-clamp recordings show that 80%-90% of AVN myocytes do not possess I(f), but nevertheless generate spontaneous action potentials with normal pacemaker depolarisations before each action potential upstroke. We have termed this type of cell "type 1". A small proportion (10%-20%) of spontaneously active AVN cells (type 2) do exhibit I(f). A 100 nM solution of isoprenaline increased the action potential rate of type 1 cells by 31%. In these cells isoprenaline did not activate any I(f) whereas in type 2 cells it clearly increased the amplitude of I(f). Manganese at 2 mM also increased the amplitude of I(f) in type 2 cells, but did not reveal I(f) in type 1 cells. We conclude that, whilst I(f) may play a role in modulating pacemaker activity in type 2 cells, in the majority of AVN cells (type 1) pacemaker depolarisation normally occurs in the complete absence of I(f). Furthermore, the inability of both isoprenaline and Mn to reveal I(f) in type 1 cells suggests that I(f) channels may be absent in these cells.