The atrioventricular node (AVN) plays an important role in the co-ordination of atrial and ventricular excitation and can act as a subsidiary pacemaker, should the sinoatrial node fail. Recent evidence suggests that Na+-dependent background current (IB,Na) is present and has the potential to play a role in determining diastolic depolarisation rate in AVN pacemaker cells (Cheng et al, 2012;2013). However, receptor-modulation of IB,Na has so far not been identified. The peptide hormone endothelin-1 (ET-1) has recently been demonstrated to modulate pacemaker activity of AVN cells (Choisy et al, 2012). In this study, the effect of ET-1 on IB,Na was studied using whole-cell patch clamp recording from isolated rabbit AVN cells.AVN cells were isolated from hearts excised from male New Zealand White rabbits (2.0-3.0 kg) using previously described methods (Hancox et al, 1993) and in accordance with UK Home Office legislation. Whole-cell patch clamp was used to record IB,Na from AVN cells at 35-37°C using a descending voltage ramp protocol from +40 mV to -100 mV, under conditions with major time and voltage-dependent conductances inhibited (Hagiwara et al, 1992). Under these conditions, the net current with a Cs+-containing pipette solution and Na+-containing external solution is a non-selective cation current (Cheng et al, 2012;2013). The external [Na+]-dependent component (IB,Na) of this net current was determined by switching between 150 mM [Na+]e and 150 mM [Tris]e (Na+-free) solutions. Two-way repeated measures ANOVA was used to compare IB,Na before and during exposure to 10nM ET-1. Values are shown as mean ± SEM. Rapid superfusion of cells with 10 nM ET-1 was found to cause a small reduction in IB,Na at voltages below -15 mV (p<0.05, n=7). At -100mV, IB,Na was 1.3±0.23 pA/pF during superfusion with control solution and -0.88±0.19 pA/pF following exposure to 10 nM ET-1. 10 nM ET-1 was also found to reduce slope conductance within the normal diastolic membrane potential range (-60 mV to -40 mV) from 0.37±0.07 nS to 0.12±0.04 nS (p<0.05). ET-1 did not have an effect on currents recorded in the absence of extracellular Na+, confirming that the modulatory effect was confined to the [Na+]e-dependent current component. To our knowledge, this is the first demonstration of direct hormonal modulation of IB,Na. Further work is now warranted to determine the mechanism of ET-1 action in relation to IB,Na and whether this current can be modulated by activation of other G-protein coupled receptors in the AVN.