K+ currents activated by leukotriene D4 or osmotic swelling in Ehrlich ascites tumour cells.

Abstract

K+ and Cl- currents activated by hypoosmotic cell swelling (IK,vol and Icl,vol) or after addition of leukotriene D4 (LTD4) to cells in isotonic medium were studied in Ehrlich ascites tumour cells. IK,vol and Icl,vol were not affected by strong buffering of intracellular Ca2+ or by additional removal of extracellular Ca2+. In isotonic media, 5 nmol/l LTD4 activated large K+ but not Cl- currents. The LTD4-activated IK was, as has been shown previously for IK,vol, insensitive to charybdotoxin (ChTX) but was blocked by the antiarrhythmic drug clofilium. The current/voltage (I/V) relation for the LTD4-activated IK was, as recently demonstrated for IK,vol, well fitted by the Goldman-Hodgkin-Katz current equation between -130 mV and 30 mV in both physiological and K+-rich extracellular solutions. LTD4 had no additional effect on the magnitude of IK in Ehrlich cells already activated by the hypoosmotic stimulus. Nevertheless, the onset time for IK after hypoosmotic cell swelling was significantly less in the presence of LTD4. The similar I/V relation, pharmacological sensitivity and lack of additivity suggest that hypoosmotic swelling and addition of LTD4 activate the same K+ channels in Ehrlich cells. The influence of [Ca2+]i appears, however, to differ between IK,vol and the IK activated by LTD4 in that the latter was reduced significantly by strong buffering of [Ca2+]i. This might reflect the involvement of some additional factor in the hypoosmotic activation of K+ channels besides the stimulation mediated by LTD4.