Selective Enhancement of the Slow Component of Delayed Rectifier K+ Current in Guinea‐Pig Atrial Cells by External ATP

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Abstract
1 The effects of external ATP on the rapidly and slowly activating components (IKr and IKg, 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 μM 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 μM)-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 IKg(V1/4 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 (IKg), with no measurable effects on IKr, in guinea-pig atrial myocytes.