Although receptors for the peptide hormone endothelin-1 (ET-1) are densely expressed in the human atrioventricular node (AVN)(Molenaar et al., 1993), there is little if any information at present regarding direct actions of ET-1 on AVN electrophysiology. The aim of the present study was to investigate the effects of ET-1 on spontaneous action potentials (APs) and ionic currents from myocytes isolated from rabbit AVN. Adult male New Zealand White rabbits were killed in accordance with UK Home Office legislation and AVN cells were isolated as described previously (Hancox et al., 1993). Spontaneous APs were recorded continuously with the gap-free acquisition mode by current clamping with a zero-current input. Membrane currents were recorded in whole-cell voltage clamp mode, with a holding potential of -40 mV to 500 ms test pulses applied to a range between -120 and +50 mV at 5 s intervals(Cheng et al., 2007). All recordings were performed at 37 °C. Data were analysed by paired Students’ t-test and a p<0.05 was considered significant. The rapid application of 10 nM ET-1 led to marked slowing of spontaneous AP rate by 47.3±5.7% (mean±SEM, n=10 cells, p<0.01). This concentration of ET-1 also hyperpolarised maximum diastolic potential by -10.3±2.0 mV (n=10, p<0.01). The amplitude of peak I_Ca at 0 mV was attenuated by 32.7±4.3% (n=10, p<0.01). Hyperpolarisation-activated current I_f at -120 mV was unaffected by ET-1 (n= 4, p>0.05). Subtraction of the quasi-steady-state (end-pulse) current in control from that in the presence of ET-1 showed that 10 nM ET-1 also activated an inwardly rectifying current that reversed at ~ -85 mV and was outwardly directed at potentials relevant to the diastolic potential range (n=8). To our best knowledge these data represent the first evidence for direct modulation of AVN cell electrophysiology by ET-1.