B. Nilius et al., PERMEATION PROPERTIES AND MODULATION OF VOLUME-ACTIVATED CL- CURRENTSIN HUMAN ENDOTHELIAL-CELLS, British Journal of Pharmacology, 112(4), 1994, pp. 1049-1056
1 We have studied the permeation and pharmacological properties of a r
ecently described volume-activated, calcium-insensitive, small-conduct
ance C1(-)-channel in endothelial cells from human umbilical vein. 2 T
he relative permeability for various anions was I->C1(-)similar to Br-
>F->gluconate(-) (1.63+/-0.36: 1:0.95+/-0.16:0.46+/-0.04:0.19+/-0.07,
n = 10). 3 5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) induced
a fast and reversible block of the current (K-I = 29 mu mol l(-1)). 4
Extracellular ATP induced a low-affinity block of the current, that s
howed a small voltage-dependence (K-I = 4.9 mmol l(-1) at +80 mV and K
-I = 8.2 mmol l(-1) at -80 mV) 5 Extracellularly applied arachidonic a
cid (10 mu mol l(-1)) irreversibly blocked the current in 5 out of 9 c
ells. This block seems to be non-specific, because other ionic current
s, e.g. inwardly rectifying K+ currents, were blocked as well. 6 Tamox
ifen induced a high affinity block of the current (K-I = 2.9 mu mol l(
-1)). Block and reversal of block were however much slower than with N
PPB. 7 Cytotoxic compounds, which are substrates of the P-glycoprotein
multidrug transporter, loaded into endothelial cells via the patch pi
pette, exerted only minor effects on the volume-activated current. Vin
blastine and colcemid did not affect the volume-activated current, whe
reas daunomycin and vincristine induced a slow 'run-down' of the curre
nt. 8 The similarity between permeation and pharmacological properties
of volume-activated Cl--currents in endothelial cells and those in ma
ny other cell types may suggest that they all belong to the same famil
y of volume-activated small-conductance Cl--channels. Evidence that th
ey belong to the class of P-glycoprotein associated Cl--channels is ho
wever only marginal, whereas their biophysical characteristics differ
significantly from those of the ClC-2 volume-activated Cl--channels.