Anion Channels

CFTR

Glycine Receptor Channel

CLC-1

Permeability Sequence for rat CLC-1 (Rychkov et al):

SCN- ∼ ClO4 − > Cl− > Br− > NO3 − ∼ ClO3 − > I− > BrO3 − > HCO3 − ∼ (F−)

The halide permeabiilty sequence of Cl− > Br− > I− suggests a strong electrostatic field at the barrier into the pore. An ion with a smaller diamter experiences a stronger force with the positive charge. The permeability of perchlorate ion suggests the minimum pore radius of ~3 Å.

Permeability sequence for human CLC-1 (Fahlke et al):

WT: Cl > thiocyanate > Br > NO3 > I > CH3SO3

G230E: thiocyanate > NO3 > I > Br > Cl > CH3SO3

The reversal of the permeability sequence suggests that the negative charge at 230 partly neutralizes the strong electrostatic positive charge at the barrier.

A recent structure of hCLC-1 revealed two chloride binding sites in the channel. The narrowest part of the pore exists between the one of the ion binding site and extracellular vestibule and is about 1.0 Å in radius. Maybe large anions such as thiocyanate and perchlorate ions wiggle through the pore with a series of induced fits. The crossing of the bottleneck by large anions may be observed in a microsecond MD simulation.

The single channel conductance of human CLC-1 is ~1 pS while that of CLC-K is ~25 pS.