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- Title
Permeant Anions Control Gating of Calcium-dependent Chloride Channels.
- Authors
P. Perez-Cornejo; J. A. De Santiago; J. Arreola
- Abstract
The effects of external anions (SCN -, NO 3-, I -, Br -, F -, glutamate, and aspartate) on gating of Ca 2+-dependent Cl - channels from rat parotid acinar cells were studied using the whole-cell configuration of the patch-clamp technique. Shifts in the reversal potential of the current induced by replacement of external Cl - with foreign anions, gave the following selectivity sequence based on permeability ratios ( P x/ P Cl): SCN ->I ->NO 3->Br ->Cl ->F ->aspartate>glutamate. Using a continuum electrostatic model we calculated that this lyotropic sequence resulted from the interaction between anions and a polarizable tunnel with an effective dielectric constant of ~23. Our data revealed that anions with P x/P Cl > 1 accelerated activation kinetics in a voltage-independent manner and slowed deactivation kinetics. Moreover, permeant anions enhanced whole-cell conductance ( g, an index of the apparent open probability) in a voltage-dependent manner, and shifted leftward the membrane potential- g curves. All of these effects were produced by the anions with an effectiveness that followed the selectivity sequence. To explain the effects of permeant anions on activation kinetics and g Cl we propose that there are 2 different anion-binding sites in the channel. One site is located outside the electrical field and controls channel activation kinetics, while a second site is located within the pore and controls whole-cell conductance. Thus, interactions of permeant anions with these two sites hinder the closing mechanism and stabilize the channel in the open state.
- Subjects
ANIONS; CELLS; FLUIDS; OSMOSIS
- Publication
Journal of Membrane Biology, 2004, Vol 198, Issue 3, p125
- ISSN
0022-2631
- Publication type
Article
- DOI
10.1007/s00232-004-0659-x