Activation of chloride current by P2-purinoceptors in rat ventricular myocytes

1. Rat ventricular myocytes were dissociated and their responses to extracellularly applied ATP were recorded using patch pipettes under the whole cell configuration. 2. ATP initially induced an inward current followed by an outward current at -50 mV. With a Cs-rich pipette solution the late outward current was blocked, leaving a sustained inward current (IATPs) suggesting that a K+ conductance underlies the late response. 3. When the extracellular Cl- concentration was changed, the reversal potential of IATPs corresponded well to the shift of the Cl- equilibrium potential. IATPs was reversibly blocked by the chloride channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS). 4. The concentration-response curve of IATPs had a Hill coefficient of 0.98 and an EC50 value of 5.2 x 10(-6) M. 5. ATP was more potent than ADP, while AMP and adenosine were ineffective, suggesting that P2-purinoceptor activation induced IATPs. 6. The activation of IATPs was depressed by depleting the extracellular Mg2+ and increased by adding Mg2+. 7. Our results strongly suggest that P2-purinoceptor activation by ATP induces both a Cl(-)-conductance (IATPs) and a K(+)-conductance in rat ventricular myocytes.