Characterisation of a cell swelling-activated K+-selective conductance of ehrlich mouse ascites tumour cells.
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. 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 (ECl) 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 approximately Na+ approximately Li+; Cs+ appeared to be inhibitory. 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. The class III antiarrhythmic drug clofilium blocked the volume-sensitive K+ current in a voltage-independent manner with an IC50 of 32 microM. Clofilium was also found to be a strong inhibitor of the regulatory volume decrease response of Ehrlich cells. 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. 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.
Niemeyer
M I
MI
Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Casilla 70058, Santiago-7, Chile.
Hougaard
C
C
Hoffmann
E K
EK
Jorgensen
F
F
Stutzin
A
A
Sepúlveda
F V
FV
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D016477:Artifacts; D002286:Carcinoma, Ehrlich Tumor / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D004558:Electric Stimulation; D004594:Electrophysiology; D007038:Hypotonic Solutions / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D007038:Hypotonic Solutions; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D011188:Potassium