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Enhancement of delayed rectifier K+ current by P2‐purinoceptor stimulation in guinea‐pig atrial cells.

1. We studied the effects of P2‐purinoceptor stimulation on the delayed rectifier K+ current (IK) in guinea‐pig atrial myocytes using a whole‐cell voltage‐clamp technique. 2. External application of ATP increased IK, evoked by a 500 ms depolarizing pulse from a holding potential of ‐40 mV, under conditions in which the L‐type Ca2+ channel was blocked; the effect was dose dependent with a half‐maximal concentration (K1/2) of 0.95 microM. ATP (50 microM) produced a maximal increase of IK of about a factor of 2. 3. External ADP also enhanced IK in a dose‐dependent manner with a K1/2 of 3.65 microM, whereas adenosine (100 microM) failed to evoke this response. Theophylline (500 microM), a blocker of the Pi‐purinoceptor, did not antagonize the stimulating action of ATP on IK. These results indicate that IK was enhanced via P2‐purinoceptors. 4. External ATP or ADP did not produce a significant change in the current kinetics of IK. 5. Pre‐incubation of the atrial myocytes with pertussis toxin (PTX, 5 micrograms ml‐1) did not affect the stimulating action of ATP on IK, indicating that PTX‐sensitive G proteins did not mediate the ATP action. 6. The enhancement of IK by ATP developed slowly; the effects usually reached a maximum approximately 30‐60 s after the application of ATP. This suggests the involvement of a diffusible cytosolic second messenger(s) in the response. ATP could further increase IK after maximal enhancement by isoprenaline (0.5‐1.0 microM), suggesting that the intermediate steps were independent of cyclic AMP‐dependent protein kinase (protein kinase A). 7. Potentiation of IK by ATP was not attenuated by either (i) pretreatment of the cells with 5 microM 1‐(5‐isoquinolinylsulphonyl)‐2‐methylpiperazine dihydrochloride (H‐7) or (ii) intracellular perfusion of 20 mM 1,2‐bis(O‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid (BAPTA), suggesting that protein kinase C and intracellular Ca2+ did not mediate the response. 8. It is concluded that the activation of P2‐purinoceptors increases IK through intracellular mechanisms independent of protein kinase A, protein kinase C or intracellular free Ca2+ in guinea‐pig atrial myocytes.