Both the rapid delayed rectifier K+ current (IKr) and muscarinic K+ current (IKACh) are present in myocytes from the rabbit atrioventricular node (AVN) (Hancox et al., 1993). Recent data indicate that both of these currents can be modulated by activation of G-protein coupled endothelin-A receptors (Choisy et al., 2012a). This study investigated whether or not an alpha-adrenoceptor agonist (phenylephrine), which also works through G-protein coupled receptor signalling pathways (Varma and Deng, 2000) is able to produce similar modulation of IKr and IKACh to that elicited by endothelin-1 (ET-1). 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). Whole-cell voltage-clamp was performed at 37 oC using a standard Tyrode’s solution and K+-based pipette solution (Choisy et al., 2012a,b). Data are presented as means ± S.E.M. and statistical comparisons made using a t-test. The amplitude of IKr tails elicited on repolarisation to -40 mV following 500 ms depolarising voltage commands to +30 mV was reduced from a mean of 2.31 ± 0.14 pA/pF by 31.2 ± 5.3 % (p<0.01 versus zero change; n=5). Instantaneous current activated by step hyperpolarisation to -120 mV from -40 mV was transiently increased ~2.5 fold from -4.07 ± 0.83 pA/pF to -10.27 ± 1.15 pA/pF (p<0.001; n=14). Repetitive application of a voltage-ramp protocol (Choisy et al., 2012b) showed that this current, which closely resembled IKACh (Choisy et al., 2012a,b) faded with a monoexponential time-course (rate constant of 0.019 ± 0.001 s−1 at -120 mV). Application of 10 μM phenylephrine (applied in the presence of 1 μM of the β1-adrenoceptor antagonist atenolol) did not produce similar effects to ET-1. Thus, in 8 cells studied, the IKr tail density elicited on repolarisation to -40 mV from +30 mV in phenylephrine was not significantly different of that in atenolol alone (an insignificant difference of +1.4 ± 8.8 % compared to atenolol alone; p>0.1; n=8). Similarly, instantaneous current activated by step hyperpolarisation to -120 mV from -40 mV in phenylephrine was not different from that in atenolol alone (99.0 ± 2.0 % of the value in atenolol alone p>0.1; n=8). We conclude that whilst ET-1 and phenylephrine are recognised to activate similar intracellular signalling pathways, under our conditions only ET-1 inhibited AVN IKr or activated an inwardly rectifying current with properties of IKACh.