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 (I-Kr and I-Ks, respectively) of the delayed rectifier K+ current (I-K) 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 a under control conditions and during exposure to 50 mu M ATP. The ATP-induced I-K, 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 I-K is due primarily to I-Ks. 3. The amplitude of I-Kr isolated from the I-K enhanced by ATP, determined as an E-4031 (5 mu M)-sensitive current, was similar to the control magnitude of I-Kr, thus showing that external,STP did not cause an increase in I-Kr. 4. The voltage-dependent activation of the ATP-induced I-K during 500 ms depolarizing test pulses could be described by a Boltzmann equation with a half-activation voltage (V-1/2) of 11.5 mV and slope factor (Ic) of 12.0 mV:, which were close to those of I-Ks (V-1/2;, of 12.1 mV and k of 12.3 mV), determined as an E-4031-resistant I-K, under the same isochronal (500 ms) activation conditions. 5. These results provide evidence to suggest that extracellular ATP selectively potentiates the slow component of I-K (I-Ks), with no measurable effects on I-Kr, in guinea-pig atrial myocytes.