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

Abstract.

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,vol and I _Cl,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,vol whereas acidification had an inhibitory effect. The magnitude of I _Cl,vol was not affected by changes in pH_i or pH_o. A significant reduction in the activation time for I _K,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,vol with respect to its pharmacological profile and current/voltage (I/V) relation. Noise analysis demonstrated that the increased amplitude of I _K,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,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.