Characterisation of a cell swelling-activated K+-selective conductance of Ehrlich mouse ascites tumour cells

1. The K+ and Cl- currents activated by hypotonic cell swelling were studied in Ehrlich ascites tumour cells using the whole-cell recording mode of the patch-clamp technique. 2. Currents were measured in the absence of added intracellular Ca2+ and with strong buffering of Ca2+. K+ current activated by cell swelling was measured as outward current at the Cl(-)equilibrium potential (E-Cl) under quasi-physiological gradients. It could be abolished by replacing extracellular Na+ with K+, thereby cancelling the driving force. Replacement with other cat;ions suggested a selectivity sequence of K+ > Rb+ > NH4 approximate to Na+ approximate to Li+; Cs+ appeared to be inhibitory. 3. The current-voltage relationship of the volume-sensitive K+ current was well fitted with the Goldman-Hodgkin-Katz current equation between -130 and +20 mV with a permeability coefficient of around 10(-6) cm s(-1) with both physiological and high-K+ extracellular solutions. 4. The class III antiarrhythmic drug clofilium blocked the volume-sensitive K+ current in a voltage-independent manner with an IC50 of 32 mu M. Clofilium was also found to be a strong inhibitor of the regulatory volume decrease response of Ehrlich cells. 5. Cell swelling-activated K+ currents of Ehrlich cells are voltage and calcium insensitive and are resistant to ct range of K+ channel inhibitors. These characteristics are similar to those of the so-called background K+ channels. 6. Noise analysis of whole-cell current was consistent with a unitary conductance of 5.5 pS for the single channels underlying the K+ current evoked by cell swelling, measured at 0 mV under a quasi-physiological K+ gradient.