Potentiation of muscarinic K⁺ channel activity by PD 81,723 in rat atrial myocytes

The 2-amino-3-benzoylthiophene derivative (PD 81,723), an allosteric enhancer of adenosine A₁ receptors, was examined with the aid of patch-clamp recording. In cell-attached configuration, adenosine and acetylcholine activated the same population of K⁺ channels that had identical conductance (28 pS) and open time (1.5 msec), i.e., acetylcholine-activated K⁺ channels (K_ACh). The addition of PD 81,723 (30 μM) or dipyridamole (30 μM) to pipette solution alone did not significantly increase the activity of K_ACh channels. The opening probability of K_ACh activity was significantly increased when pipette solution contained adenosine (10 μM) plus PD 81,723 (10 μM) in comparison with that containing adenosine (10 μM) alone (0.43 vs. 0.24). The activity of K_ACh channels induced by acetylcholine between the absence and presence of PD 81,723 did not differ. The EC₅₀ value for the effect of adenosine on K_ACh activity between the absence and presence of PD 81,723 was 6 μM vs. 2 μM. The single channel conductance and open time of K_ACh remained unchanged when both adenosine and PD 81,723 were included into the pipette. Thus, PD 81,723 can facilitate the opening of K_ACh channels by adenosine, not by acetylcholine. The kinetic activity of K_ACh channels per se was not altered by PD 81,723. And the opening activity of K_ACh channels was unaffected by endogenous adenosine plus PD 81,723.