Further analysis of counterion permeation through anion-selective glycine receptor channels

Abstract

The functional role of ion channels, which allow counterion permeation, depends critically on their relative anion-cation relative selectivity. From whole-cell patch clamp reversal potential measurements under dilution potential conditions, we have already shown that anion-cation permeabilities of anion-selective wild-type (WT) and mutant (with larger pore diameter) glycine receptor (GlyR) channels in the presence of Li(+), Na(+) and Cs(+) counterions, were inversely correlated with the equivalent hydration diameter of the counterion, with chloride-cation permeability increasing as counterion equivalent hydration diameter increased with respect to the channel minimum pore diameter. Corrected for liquid junction potentials (LJPs; using ion activities), the previous chloride-cation permeabilities for the alkali cations were 23.4 (Li(+)), 10.9 (Na(+)) and 5.0 (Cs(+)) for the smaller WT channel. Further analysis to incorporate an initial offset potential correction, to fully allow for slight differences between internal cell composition and external control salt solution, changed the above permeability ratios to 30.6 (Li(+)), 11.8 (Na(+)) and 5.0 (Cs(+)), adding enhanced support for the inverse correlation between anion-to-counterion permeability ratio and equivalent hydrated counterion diameter relative to channel pore diameter (erroneously ignoring LJPs reduces each permeability ratio to about 4). Also, new direct measurements of LJPs (for NaCl and LiCl salt dilutions) using a 3M KCl-agar reference salt bridge (with freshly-cut end for each solution composition change) have shown excellent agreement with calculated LJPs (using ion activities), validating calculated LJP values. We continue to suggest that counterion cations permeate with chloride ions as neutral pairs.

Counterion-Assisted Cation Transport in a Biological Calcium Channel

“…A possible reason is that many channels are selective for a specific ion (typically a cation), and counterions do not seem vital to the conduction mechanism. A few exceptions to this paradigm are available, including the chloride channel, the OmpF porin, the KAT1 channel (a voltage-gated K + channel from Arabidopsis thaliana ), and the glycine receptor, − as well as synthetic cation-selective nanotubes mimicking a biological ion channel . Among these few examples, the permeability of counterions has been partially characterized, suggesting a possible functional role.…”

Synthetic cation-selective nanotube: Permeant cations chaperoned by anions

“…Once inside the nanotube these resident chloride ions act to ferry, or chaperone, sodium ions from the entrance to the exit of the nanotube. This artificial channel resembles that of the mutant glycine receptor 38 in which anions act to chaperone sodium ions 40,41 with a conductance of 17 pS.…”

Channels: The first five years

“…This includes several articles in the area of Stim/Orai, 1,2 which interestingly are among the highest cited Channels articles. Other areas covered in channels included ligand-gated channels, [3][4][5][6][7] potassium channels, [8][9][10][11] voltage-gated calcium and sodium channels, 12-15 and transporters, [16][17][18][19] among many others too numerous to list here. While a number of articles dealt with structure, function and regulation of ion channels and transporters, many papers were focused on the role of ion channels in mammalian physiology such as neurological and cardiovascular disorders.…”