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Anomalous effect of anthracene-9-carboxylic acid on calcium-activated chloride currents in rabbit pulmonary artery smooth muscle cells.

Abstract：

:1 Ca(2+)-activated Cl(-) currents (I(Cl(Ca))) evoked by K(+)-free pipette solutions containing 500 nM Ca(2+) were recorded in rabbit pulmonary artery smooth muscle cells. A voltage step protocol in which the cells were stepped to +70 mV and then to -80 mV produced outward and inward Cl(-) currents respectively that exhibited distinctive voltage- and time-dependent kinetics that remained consistent for the recording period. 2 Application of the Cl(-) channel inhibitor anthracene-9-carboxylic acid (A-9-C, 500 micro M), produced a small inhibition of the maximum outward Cl(-) current at +70 mV (21+/-10%) but augmented the amplitude of the instantaneous inward relaxation at -80 mV by 321+/-34% (n=12). 3 The current recorded in the absence and presence of A-9-C reversed at the theoretical Cl(-) equilibrium potential and the reversal potential was shifted by about -40 mV upon replacement of external chloride ion by the more permeant anion thiocyanate. Currents in the absence and presence of A-9-C were similarly affected by 100 micro M niflumic acid. 4 Augmentation of the inward current at -80 mV by A-9-C required prior depolarization, i.e. A-9-C did not simply activate a Cl(-) current at negative membrane potentials. Moreover the degree of augmentation was independent of the internal Ca(2+) for concentrations between 100 nM and 1 micro M Ca(2+). 5 The data from the present study confirm previous observations that the inhibitory effect of Cl(-) channel blockers is modified when [Ca(2+)](i) is maintained at higher than normal resting concentrations.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Piper AS,Greenwood IA

doi

10.1038/sj.bjp.0705000

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

31-8

issue

1

eissn

0007-1188

issn

1476-5381

journal_volume

138

pub_type

杂志文章

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