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

María Isabel Niemeyer *³, Charlotte Hougaard ¹, Else K. Hoffmann ¹, Finn Jørgensen ², Andrés Stutzin * and Francisco V. Sepúlveda *³

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 cations suggested a selectivity sequence of K⁺ > Rb⁺ > NH₄ Na⁺ 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 µM. 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 a 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.

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