The peptide hormone endothelin-1 (ET-1) is produced constitutively within the heart and modulates cardiac function in a paracrine/autocrine fashion (Russell & Molenaar, 2000). The effects of ET-1 may be mediated via activation of ETA and/or ETB receptors, both of which are present in the human atrioventricular node (AVN; Molenaar et al., 1993). A recent pilot study has demonstrated a direct effect of ET-1 on AVN cellular electrophysiology (Cheng et al., 2008), although not the receptor type involved. This study was undertaken, therefore, to investigate effects on the cellular electrophysiology of the AVN of selected ETA and ETB receptor ligands. Adult male New Zealand White rabbits were killed in accord with UK Home Office legislation, and cells were isolated from the AVN as previously described (Hancox et al., 1993). Whole-cell patch-clamp recordings were performed at 37°C using a standard Tyrode’s solution and K+-based pipette solution. Ionic currents were elicited using 500 ms duration test-pulses to voltages ranging from −120 to +50 mV from a holding potential of −40 mV. Experiments employed 10 nM ET-1, 300 nM IRL-1620 (a selective ETB receptor agonist) or 1 μM BQ-123 (a selective ETA receptor antagonist). Concordant with our previous findings (Cheng et al., 2008), 10 nM ET-1 reduced the amplitude of both L-type Ca current (ICa,L) and delayed rectifier (IK) ‘tails’, whereas, at steady-state, the amplitude of the hyperpolarisation-activated current (If) was not significantly altered. If was not modified by either IRL-1620 or BQ-123. Application of IRL-1620 alone significantly reduced ICa,L amplitude at voltages between −10 to +40 mV (n=6; P<0.05, two-way ANOVA) with ICa,L density at +10 mV being decreased by 60 ± 9 % (n=6). This compared to a 74 ± 6 % decrease caused by ET-1 alone at the same voltage (n=11; not significantly different). In contrast, IRL-1620 did not significantly reduce IK tail amplitude (measured at −40 mV following voltage commands to between −30 mV and +50 mV; P>0.05). Application of BQ-123 alone reduced the amplitude of ICa,L (by 54 ± 9% at +10 mV; n=5); subsequent application of ET-1 then had no significant effect on peak ICa,L at +10 mV (n=5). BQ-123 had no effect on IK tail amplitude when applied alone; however, it prevented modulation by subsequent ET-1 application. These results raise the possibility of differential ET receptor modulation of ICa,L and IK: both ETA and ETB receptor ligands affected AVN ICa,L modulation, whereas ET-1 actions on IK might involve ETA receptors alone. The potential for non-specific effects (unrelated to ET-1 receptor blockade) of the agents studied warrants further future investigation with additional ETA and ETB ligands.