PMID- 20198385
OWN - NLM
STAT- MEDLINE
DCOM- 20100824
LR  - 20211020
IS  - 1432-2013 (Electronic)
IS  - 0031-6768 (Linking)
VI  - 460
IP  - 1
DP  - 2010 Jun
TI  - External divalent cations increase anion-cation permeability ratio in glycine 
      receptor channels.
PG  - 131-52
LID - 10.1007/s00424-010-0792-6 [doi]
AB  - The functional role of ligand-gated ion channels in the central nervous system 
      depends on their relative anion-cation permeability. Using standard whole-cell 
      patch clamp measurements and NaCl dilution potential measurements, we explored 
      the effect of external divalent ions on anion-cation selectivity in 
      alpha1-homomeric wild-type glycine receptor channels. We show that increasing 
      external Ca(2+) from 0 to 4 mM resulted in a sigmoidal increase in anion-cation 
      permeability by 37%, reaching a maximum above about 2 mM. Our accurate 
      quantification of this effect required rigorous correction for liquid junction 
      potentials (LJPs) using ion activities, and allowing for an initial offset 
      potential. Failure to do this results in a considerable overestimation of the 
      Ca(2+)-induced increase in anion-cation permeability by almost three-fold at 4 mM 
      external Ca(2+). Calculations of LJPs (using activities)_ were validated by 
      precise agreement with direct experimental measurements. External SO (4) (2-) was 
      found to decrease anion-cation permeability. Single-channel conductance 
      measurements indicated that external Ca(2+) both decreased Na(+) permeability and 
      increased Cl(-) permeability. There was no evidence of Ca(2+) changing channel 
      pore diameter. Theoretical modeling indicates that the effect is not surface 
      charge related. Rather, we propose that, under dilution conditions, the presence 
      of an impermeant Ca(2+) ion in the channel pore region just external to the 
      selectivity filter tends to electrostatically retard outward movement of Na(+) 
      ions and to enhance movement of Cl(-) ions down their energy gradients.
FAU - Sugiharto, Silas
AU  - Sugiharto S
AD  - Department of Physiology, School of Medical Sciences, University of New South 
      Wales, Sydney, NSW, 2052, Australia.
FAU - Carland, Jane E
AU  - Carland JE
FAU - Lewis, Trevor M
AU  - Lewis TM
FAU - Moorhouse, Andrew J
AU  - Moorhouse AJ
FAU - Barry, Peter H
AU  - Barry PH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100303
PL  - Germany
TA  - Pflugers Arch
JT  - Pflugers Archiv : European journal of physiology
JID - 0154720
RN  - 0 (Chlorides)
RN  - 0 (Receptors, Glycine)
RN  - 0 (Sulfates)
RN  - 9NEZ333N27 (Sodium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cell Membrane/*metabolism
MH  - *Cell Membrane Permeability
MH  - Chlorides/metabolism
MH  - Humans
MH  - *Ion Channel Gating
MH  - Membrane Potentials
MH  - Models, Theoretical
MH  - Patch-Clamp Techniques
MH  - Receptors, Glycine/genetics/*metabolism
MH  - Reproducibility of Results
MH  - Sodium/metabolism
MH  - Sulfates/metabolism
MH  - Transfection
EDAT- 2010/03/04 06:00
MHDA- 2010/08/25 06:00
CRDT- 2010/03/04 06:00
PHST- 2009/11/26 00:00 [received]
PHST- 2010/01/22 00:00 [accepted]
PHST- 2010/01/15 00:00 [revised]
PHST- 2010/03/04 06:00 [entrez]
PHST- 2010/03/04 06:00 [pubmed]
PHST- 2010/08/25 06:00 [medline]
AID - 10.1007/s00424-010-0792-6 [doi]
PST - ppublish
SO  - Pflugers Arch. 2010 Jun;460(1):131-52. doi: 10.1007/s00424-010-0792-6. Epub 2010 
      Mar 3.