ACTIVATION OF POTASSIUM CURRENTS BY INHIBITORS OF CALCIUM-ACTIVATED CHLORIDE CONDUCTANCE IN RABBIT PORTAL-VEIN SMOOTH-MUSCLE CELLS

Citation
C. Toma et al., ACTIVATION OF POTASSIUM CURRENTS BY INHIBITORS OF CALCIUM-ACTIVATED CHLORIDE CONDUCTANCE IN RABBIT PORTAL-VEIN SMOOTH-MUSCLE CELLS, British Journal of Pharmacology, 118(3), 1996, pp. 513-520
Citations number
22
Categorie Soggetti
Pharmacology & Pharmacy",Biology
ISSN journal
00071188
Volume
118
Issue
3
Year of publication
1996
Pages
513 - 520
Database
ISI
SICI code
0007-1188(1996)118:3<513:AOPCBI>2.0.ZU;2-4
Abstract
1 The conventional whole-cell recording technique was used to study th e effects of the chloride channel inhibitors ethacrynic acid, anthrace ne-9-carboxylic acid (A-9-C) and indanyloxyacetic acid (IAA) on membra ne currents in rabbit portal vein smooth muscle cells at a holding pot ential of 0 mV. 2 Using a pipette solution that contained 1 x 10(-4) M 1,2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) an d a normal bathing solution the addition of ethacrynic acid (2 x 10(-4 ) M to 1 x 10(-3) M) inhibited spontaneous transient outward currents (STOCs) and evoked a concentration-dependent current at a holding pote ntial of 0 mV. A similar current was activated by IAA (5 x 10(-4) M to 1 x 10(-3) M) but not by A-9-C (1-5 x 10(-3) M) at a holding potentia l of 0 mV. 3 The amplitude of the current evoked by ethacrynic acid an d IAA was linearly related to potential between -30 and 0 mV and displ ayed outward rectification at positive potentials. The current induced by A-9-C was evident only at potentials positive to +20 mV. 4 Glibenc lamide (1 x 10(-5) M) abolished the current evoked by ethacrynic acid and IAA at potentials negative to +10 mV and partially inhibited the c urrent positive to +10 mV. The glibenclamide-insensitive current at po sitive potentials was completely inhibited by 1 x 10(-3) M TEA. The A- g-C-evoked current was insensitive to glibenclamide and abolished by 1 x 10(-3) M TEA. 5 The glibenclamide-sensitive current activated by et hacrynic acid was not sustained and declined to control levels in the continued presence of ethacrynic acid. However, the outwardly rectifyi ng 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 x 10(-2) M BAPTA in cells bathed in Ca-free extracellular solution containing 5 x 10(-4) M BAPTA and 1 x 10(-5) M cyclopiazonic acid. 7 It is concluded that al l three chloride-channel blockers activated an outwardly rectifying, T EA-sensitive current. Moreover, ethacrynic acid and IAA evoked an addi tional glibenclamide-sensitive current which was present at all potent ials between -30 and +50 mV.