Anomalous effect of anthracene-9-carboxylic acid on calcium-activated chloride currents in rabbit pulmonary artery smooth muscle cells.
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.
Piper
Angela S
AS
Department of Pharmacology & Clinical Pharmacology, St George's Hospital Medical School, London, SW17 0RE, UK.
Greenwood
Iain A
IA
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits
D000873:Anthracenes; D018118:Chloride Channels; C010030:9-anthroic acid; D002118:Calcium