Selective enhancement of the slow component of delayed rectifier K+ current in guinea-pig atrial cells by external ATP.

1. The effects of external ATP on the rapidly and slowly activating components (IKr and IKs, respectively) of the delayed rectifier K+ current (IK) in guinea-pig atrial myocytes were determined using the whole-cell configuration of the patch-clamp technique. 2. An envelope of tails test was conducted by applying depolarizing pulses to +40 mV from a holding potential of -40 mV for various durations between 50 ms and 2 s under control conditions and during exposure to 50 microM ATP. The ATP-induced IK, obtained by digital subtraction, exhibited a constant ratio (0.37) of the tail current to time-dependent current, regardless of the pulse duration. This current ratio was compatible with the predicted ratio of the driving force at +40 and -40 mV for a non-rectifying K+ conductance, suggesting that the ATP-induced IK is due primarily to IKs. 3. The amplitude of IKr isolated from the IK enhanced by ATP, determined as an E-4031 (5 microM)-sensitive current, was similar to the control magnitude of IKr, thus showing that external ATP did not cause an increase in IKr. 4. The voltage-dependent activation of the ATP-induced IK during 500 ms depolarizing test pulses could be described by a Boltzmann equation with a half-activation voltage (V1/2) of 11.5 mV and slope factor (k) of 12.0 mV, which were close to those of IKs (V1/2 of 12.1 mV and k of 12.3 mV), determined as an E-4031-resistant IK, under the same isochronal (500 ms) activation conditions. 5. These results provide evidence to suggest that extracellular ATP selectively potentiates the slow component of IK (IKs), with no measurable effects on IKr, in guinea-pig atrial myocytes.