K+ conductance activated during regulatory volume decrease. The channels in Ehrlich cells and their possible molecular counterpart

K+ currents activated by hypotonic cell swelling have been studied in Ehrli ch ascites tumour cells by the whole-cell recording mode of the patch-clamp technique. K+ together with Cl- currents developed in the absence of added intracellular Ca2+ and with strong buffering of internal Ca2+ in experimen ts conducted at 37 degreesC. Manipulation of the extracellular medium with other cations suggests a selectivity sequence of K+ > Rb+ > NH4+ greater th an or equal to Na+ congruent to Li+ congruent to Cs+. The current-voltage r elationship of the volume-sensitive K+ current was well fitted with the Gol dman-Hodgkin-Katz current equation between - 130 and 20 mV at both physiolo gical and high K+ extracellular solutions. The class III antiarrhytmic drug clofilium blocked the volume-sensitive K+ current in a voltage-independent manner. Clofilium was also found to be a strong inhibitor of the regulator y volume decrease (RVD) response of Ehrlich cells. The leukotriene D-4 (LTD 4) can activate the same current in isotonicity, consistent with a role for this compound in the signalling process of volume regulation. It is sugges ted that K+ channels activated by cell swelling belong to the so-called bac kground K+ channel group. These are voltage-independent channels which unde rlie the resting potential of many cells and have recently been identified as belonging to a family of K+ channels with two pore domains in tandem (2P -4TM). Preliminary experiments show the presence of the TASK-2 channel, a m ember of the 2P-4TM family inhibited by acid extracellular pH, in Ehrlich c ells and suggest that it might underlie the swelling-induced K+ current. (C ) 2001 Elsevier Science Inc. All rights reserved.