Modulation of Voltage-dependent Properties of a Swelling-activated Cl(−) Current

We used the patch-clamp technique to study the voltage-dependent properties of the swelling-activated Cl(−) current (I (Cl,swell)) in BC(3)H1 myoblasts. This Cl(−) current is outwardly rectifying and exhibits time-dependent inactivation at positive potentials (potential for half-maximal inactivation of +75 mV). Single-channel Cl(−) currents with similar voltage-dependent characteristics could be measured in outside-out patches pulled from swollen cells. The estimated single-channel slope conductance in the region between +60 and +140 mV was 47 pS. The time course of inactivation was well described by a double exponential function, with a voltage-independent fast time constant (∼60 ms) and a voltage-dependent slow time constant (>200 ms). Recovery from inactivation, which occurred over the physiological voltage range, was also well described by a double exponential function, with a voltage-dependent fast time constant (10–80 ms) and a voltage-dependent slow time constant (>100 ms). The inactivation process was significantly accelerated by reducing the pH, increasing the Mg(2+) concentration or reducing the Cl(−) concentration of the extracellular solution. Replacing extracellular Cl(−) by other permeant anions shifted the inactivation curve in parallel with their relative permeabilities (SCN(−) > I(−) > NO(3) (−) > Cl(−) >> gluconate). A leftward shift of the inactivation curve could also be induced by channel blockers. Additionally, the permeant anion and the channel blockers, but not external pH or Mg(2+), modulated the recovery from inactivation. In conclusion, our results show that the voltage-dependent properties of I (Cl,swell) are strongly influenced by external pH , external divalent cations, and by the nature of the permeant anion.