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) respecti vely) on the regulatory volume decrease (RVD) response and on the volume-se nsitive K+ and Cl- currents (I-K,I-vol and I-Cl,I-vol respectively) were st udied in Ehrlich ascites tumour cells. Alkaline pH(o) accelerated and acidi c pH(o) decelerated the RVD response significantly. Intra- and extracellula r 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 f or I-K,I-vol after hypotonic cell swelling was observed upon moderate intra cellular 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 c urrent/voltage (I/V) relation. Noise analysis demonstrated that the increas ed amplitude of I-K,I-vol at alkaline pH resulted mainly from an increase i n 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 b iophysical 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.