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Effects of Cl channel blockers on Ca‐activated chloride and potassium currents in smooth muscle cells from rabbit portal vein
Author(s) -
Hogg R.C.,
Wang Q.,
Large W.A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14891.x
Subject(s) - dids , chemistry , calcium , potassium , biophysics , chloride channel , chloride , tetraethylammonium chloride , caffeine , potassium channel , biochemistry , medicine , organic chemistry , membrane , biology
1 The effects of some chloride channel antagonists were studied on the calcium‐activated chloride current ( I Cl(ca) ) in smooth muscle cells from the rabbit portal vein with the perforated patch technique. 2 4‐Acetamido‐4′‐isothiocyanatostilbene‐2,2′‐disulphonic acid (SITS) and 4,4′‐diisothiocyanato‐stilbene‐2,2′‐disulphonic acid (DIDS) reduced the amplitude of spontaneous transient inward currents (STICs, calcium‐activated chloride currents) in a concentration‐dependent manner. The concentrations required to reduce the amplitude by 50% (IC 50 ) of STICs were 2.1 × 10 −4 m and 6.4 × 10 −4 m for DIDS and SITS, respectively. This effect was not voltage‐dependent. 3 The time constant of decay of STICs (τ), which is voltage‐dependent, was increased by about 30% by SITS and decreased by about 20% by DIDS. The effect of DIDS and SITS on τ was similar at holding potentials of − 50 and + 50 mV. 4 These compounds did not modify the characteristics of spontaneous transient outward currents (STOCs, calcium‐activated potassium currents). 5 DIDS and SITS decreased the amplitude of I Cl(Ca) evoked by noradrenaline and caffeine less potently than STICs with IC 50 values of 7.5 × 10 −4 m and 1.8 × 10 −3 m , respectively. 6 DIDS and SITS increased the calcium‐activated potassium current ( I K(Ca) ) evoked by noradrenaline and caffeine by 3–6 fold. 7 Anthracene‐9‐carboxylic acid (A‐9‐C) inhibited STICs in a voltage‐dependent fashion and was about 3 fold more active at + 50 mV than at − 50 mV. A‐9‐C increased STIC τ and this effect was enhanced by depolarization. 8 A‐9‐C also inhibited caffeine‐evoked I Cl(ca) but less potently than STICs and also increased the evoked I K(ca) without altering spontaneous I K(ca) . 9 The results from the present work are compared with the pharmacology of other chloride conductances and the mechanism of action of the chloride channel antagonists in vascular smooth muscle is discussed.