Modulation of the volume-sensitive K+ current in Ehrlich ascites tumour cells by pH

The effects of extracellular and intracellular pH (pH(o) and pH(i) respectively) on the regulatory volume decrease (RVD) response and on the volume-sensitive K+ and Cl- currents (I-K,I-vol and I-Cl,I-vol respectively) were studied in Ehrlich ascites tumour cells. Alkaline pH(o) accelerated and acidic pH(o) decelerated the RVD response significantly. Intra- and extracellular alkalinisation increased the amplitude of I-K,I-vol whereas acidification had an inhibitory effect. The magnitude of I-Cl,I-vol was not affected by changes in pH(i) or pH(o). A significant reduction in the activation time for I-K,I-vol after hypotonic cell swelling was observed upon moderate intracellular alkalinisation (to pH(i) 7.9). A further increase in pH(i) to 8.4 resulted in the spontaneous activation of an I-K under isotonic conditions which resembled I-K,I-vol with respect to its pharmacological profile and current/voltage (I/V) relation. Noise analysis demonstrated that the increased amplitude of I-K,I-vol at alkaline pH resulted mainly from an increase in the number of channels (N) contributing to the current. The channel open probability, P-o, was largely unaffected by pH. The pH dependence and the biophysical and pharmacological properties of I-K,I-vol are similar to those of the cloned tandem pore-domain acid-sensitive K+ (TASK) channels, and in the current study the presence of TASK-1 was confirmed in Ehrlich cells.