Effect of frusemide, ethacrynic acid and indanyloxyacetic acid on spontaneous Ca-activated currents in rabbit portal vein smooth muscle cells.
1. The effect of frusemide, ethacrynic acid and indanyloxyacetic acid was investigated on spontaneous calcium-activated chloride (ICl(Ca)) and potassium currents (IK(Ca)) in rabbit portal vein cells with the perforated patch technique. 2. Frusemide (0.3-1.0 x 10(-3) M) reduced the amplitude of spontaneous transient inward chloride currents (STICs) in a concentration-dependent manner. The degree of inhibition on STIC amplitude was similar between -50 and +30 mV and frusemide did not alter the STIC reversal potential (Erev). 3. The voltage-dependent exponential decay of STICs, which is thought to represent closure of chloride channels, was not altered by frusemide. 4. The amplitude and frequency of spontaneous potassium outward currents (STOCs) were not altered by frusemide. Since both STICs and STOCs are activated by calcium released from intracellular stores these data indicate that frusemide may block directly ICl(Ca). 5. Ethacrynic acid (2-5 x 10(-4) M) decreased the amplitude of STICs in a concentration-dependent manner by a similar amount at potentials of -50 to +30 mV but did not alter the STIC Erev. However, these concentrations of ethacrynic acid also reduced STOC amplitude and 5 x 10(-4) M ethacrynic acid evoked a sustained outward current in most cells at 0 mV; thus ethacrynic acid has a more complex action than simple block of ICl(Ca). 6. Indanyloxyacetic acid reduced both STIC amplitude and decay time without affecting STOCs and thus also seems to inhibit directly ICl(Ca). It is discussed whether block of ICl(Ca) mediates the vasodilator effect of these agents.
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London.
I A
IA
Greenwood
R C
RC
Hogg
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Large
D000818:Animals; D002118:Calcium / Q000502:physiology*; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006016:Glycolates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits
D018118:Chloride Channels; D004232:Diuretics; D006016:Glycolates; D007473:Ion Channels; D015221:Potassium Channels; C015765:MK 473; D005665:Furosemide; D004976:Ethacrynic Acid; D002118:Calcium