title: Protons and calcium alter gating of the hyperpolarization-activated cation current (I(h)) in rod photoreceptors.
abstract: We investigated the effects of protons and calcium ions on the voltage-dependent gating of the hyperpolarization-activated, nonselective cation channel current, I(h), in rod photoreceptors. I(h) is a cesium-sensitive current responsible for the peak-plateau sag during the rod response to bright light. The voltage dependence of I(h) activation shifted about 5 mV per pH unit, with external acidification producing positive shifts and alkalinization producing negative shifts. Increasing external [Ca(2+)] from 3 to 20 mM resulted in a large (approximately 17 mV) positive shift in I(h) activation. External [Ca(2+)] (20 mM) blocked pH-induced shifts in activation. Cytoplasmic acidification produced by 25 mM sodium acetate led to a negative shift in inactivation (-9 mV) and internal alkalinization produced with 20 mM ammonium chloride resulted in a positive shift (+6 mV). Surface charge binding and screening theory (Gouy-Chapman-Stern) accounted for the observed shifts in I(h) activation, with the best fit achieved when protons and calcium ions were assumed to bind to distinct sites on the membrane. Since light induces changes in the retinal ionic environment, these results permit us to gauge the degree to which rod light responses could be modified via alterations in I(h) activation.
authors.affiliation: Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Andrew Todd
authors.initials: AT
authors.lastname: Malcolm
authors.forename: Dmitri E
authors.initials: DE
authors.lastname: Kourennyi
authors.forename: Steven
authors.initials: S
authors.lastname: Barnes
mesh_terms: D000557:Ambystoma; D000643:Ammonium Chloride; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent; D054815:Cyclic Nucleotide-Gated Cation Channels; D006863:Hydrogen-Ion Concentration; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008027:Light; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D011522:Protons; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D019346:Sodium Acetate
chemical_list: D002413:Cations, Divalent; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011522:Protons; D000643:Ammonium Chloride; D019346:Sodium Acetate; D002118:Calcium