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 Ehrlich 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 experiments conducted at 37 degrees C. Manipulation of the extracellular medium with other cations suggests a selectivity sequence of K+ > Rb+ > NH4+ > or = Na+ approximately equals Li+ approximately equals Cs+. 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 at both physiological 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 regulatory volume decrease (RVD) response of Ehrlich cells. The leukotriene D4 (LTD4) can activate the same current in isotonicity, consistent with a role for this compound in the signalling process of volume regulation. It is suggested that K+ channels activated by cell swelling belong to the so-called background K+ channel group. These are voltage-independent channels which underlie 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 member of the 2P-4TM family inhibited by acid extracellular pH, in Ehrlich cells and suggest that it might underlie the swelling-induced K+ current.
Niemeyer
M I
MI
Centro de Estudios Científicos (CECS), Valdivia, Chile. miniemeyer@cecs.cl
Cid
L P
LP
Sepúlveda
F V
FV
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D048429:Cell Size; D004247:DNA; D006801:Humans; D017136:Ion Transport; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain; D014407:Tumor Cells, Cultured
C410295:KCNK5 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D004247:DNA; D011188:Potassium