Activation of potassium currents by inhibitors of calcium‐activated chloride conductance in rabbit portal vein smooth muscle cells

• Published in: British journal of pharmacology 1996-06, Vol.118 (3), p.513-520
• Main Authors: Toma, C., Greenwood, I.A., Helliwell, R.M., Large, W.A.
• Format: Article
• Language: English
• Subjects: Animals; anthracene‐9‐carboxylic acid; Biological and medical sciences; Cardiovascular system; chloride channel blockers; Chloride Channels - antagonists & inhibitors; Dose-Response Relationship, Drug; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; ethacrynic acid; Ethacrynic Acid - pharmacology; Female; indanyloxyacetic acid; Medical sciences; Membrane Potentials - drug effects; Miscellaneous; Muscle, Smooth, Vascular - drug effects; Pharmacology. Drug treatments; Portal Vein - drug effects; Potassium Channels - drug effects; Potassium currents; Rabbits; vascular smooth muscle
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15432.x

1 The conventional whole‐cell recording technique was used to study the effects of the chloride channel inhibitors ethacrynic acid, anthracene‐9‐carboxylic acid (A‐9‐C) and indanyloxyacetic acid (IAA) on membrane currents in rabbit portal vein smooth muscle cells at a holding potential of 0 mV. 2 Using a pipette solution that contained 1 × 10−4 m 1, 2‐bis (2‐aminophenoxy)‐ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA) and a normal bathing solution the addition of ethacrynic acid (2 × 10−4 m to 1 × 10−3 m) inhibited spontaneous transient outward currents (STOCs) and evoked a concentration‐dependent current at a holding potential of 0 mV. A similar current was activated by IAA (5 × 10−4 m to 1 × 10−3 m) but not by A‐9‐C (1–5 × 10−3 m) at a holding potential of 0 mV. 3 The amplitude of the current evoked by ethacrynic acid and IAA was linearly related to potential between −30 and 0 mV and displayed outward rectification at positive potentials. The current induced by A‐9‐C was evident only at potentials positive to +20 mV. 4 Glibenclamide (1 × 10−5 m) abolished the current evoked by ethacrynic acid and IAA at potentials negative to +10 mV and partially inhibited the current positive to +10 mV. The glibenclamide‐insensitive current at positive potentials was completely inhibited by 1 × 10−3 m TEA. The A‐9‐C‐evoked current was insensitive to glibenclamide and abolished by 1 × 10−3 m TEA. 5 The glibenclamide‐sensitive current activated by ethacrynic acid was not sustained and declined to control levels in the continued presence of ethacrynic acid. However, the outwardly rectifying current recorded at +50 mV was well maintained over the same period. 6 Outwardly rectifying currents evoked by ethacrynic acid and A‐9‐C were observed with a pipette solution containing 1 × 10−2 m BAPTA in cells bathed in Ca‐free extracellular solution containing 5 × 10−4 m BAPTA and 1 × 10−5 m cyclopiazonic acid. 7 It is concluded that all three chloride‐channel blockers activated an outwardly rectifying, TEA‐sensitive current. Moreover, ethacrynic acid and IAA evoked an additional glibenclamide‐sensitive current which was present at all potentials between −30 and +50 mV.