Ion selectivity predictions from a two-site permeation model for the cyclic nucleotide-gated channel of retinal rod cells.
We developed a two-site, Eyring rate theory model of ionic permeation for cyclic nucleotide-gated channels (CNGCs). The parameters of the model were optimized by simultaneously fitting current-voltage (IV) data sets from excised photoreceptor patches in electrolyte solutions containing one or more of the following ions: Na+, Ca2+, Mg2+, and K+. The model accounted well for 1) the shape of the IV relations; 2) the binding affinity for Na+; 3) reversal potential values with single-sided additions of Ca2+ or Mg2+ and biionic KCl; and 4) the K1 and voltage dependence for divalent block from the cytoplasmic side of the channel. The differences between the predicted K1's for extracellular block by Ca2+ and Mg2+ and the values obtained from heterologous expression of only the alpha-subunit of the channel suggest that the beta-subunit or a cell-specific factor affects the interaction of divalent cations at the external but not the internal face of the channel. The model predicts concentration-dependent permeability ratios with single-sided addition of Ca2+ and Mg2+ and anomalous mole fraction effects under a limited set of conditions for both monovalent and divalent cations. Ca2+ and Mg2+ are predicted to carry 21% and 10%, respectively, of the total current in the retinal rod cell at -60 mV.
Wells
G B
GB
Department of Pathology, School of Medicine, University of Pennsylvania, Philadelphia 19104-6002, USA.
Tanaka
J C
JC
D000557:Ambystoma; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002463:Cell Membrane Permeability; D006152:Cyclic GMP / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D046911:Macromolecular Substances; D008274:Magnesium / Q000494:pharmacology; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D011894:Rana pipiens; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology
D007473:Ion Channels; D046911:Macromolecular Substances; D011189:Potassium Chloride; D012964:Sodium; D006152:Cyclic GMP; D008274:Magnesium; D002118:Calcium