title: Suppression by an h current of spontaneous Na+ action potentials in human cone and rod photoreceptors.
abstract: OBJECTIVE
  The sense of vision in humans is robust, and visual flickering is rarely experienced. To investigate this mechanism, electrophysiological and molecular biological techniques were used on human cone and rod photoreceptors.
  
  
  METHODS
  Voltage-gated currents were recorded using the patch-clamp technique on isolated human cones, and especially their voltage-gated Na+ currents were analyzed in detail. Whether Na+ channel transcripts could be detected in single photoreceptors using RT-PCR was also examined, to test the expression of voltage-gated Na+ channels in cones and/or rods.
  
  
  RESULTS
  Under current-clamp conditions, blocking h currents (hyperpolarization-activated cationic currents) with Cs+, Tl+, or ZD7288 hyperpolarized the resting potentials of cones and rods by approximately 10 to 15 mV, and surprisingly generated spontaneous action potentials. The spontaneous spikes were blocked by 1 microM tetrodotoxin, but not by 1 mM Co2+, suggesting that they were Na+ spikes rather than Ca2+ spikes. Under voltage-clamp conditions, application of Cs+ and ZD7288 markedly decreased the steady inward current through the h channel. This is consistent with Cs+-induced hyperpolarization under a current-clamp condition. SCN2 Na+ channel was observed in both cones and rods by single-cell RT-PCR analysis, suggesting that human photoreceptors express the SCN2 Na+ channel.
  
  
  CONCLUSIONS
  The data confirmed that voltage-gated Na+ channels were expressed not only in human rods but also in cones by electrophysiological and molecular biological experiments. These results suggest that the h current may contribute to preventing visual flickering by inhibiting the generation of spontaneous Na+ spikes in human photoreceptors.
authors.affiliation: Department of Physiology, School of Medicine, Fujita Health University, Aichi, Japan. fkawai@fujita-hu.ac.jp
authors.forename: Fusao
authors.initials: F
authors.lastname: Kawai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Horiguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichinose
authors.forename: Mahito
authors.initials: M
authors.lastname: Ohkuma
authors.forename: Ryoko
authors.initials: R
authors.lastname: Isobe
authors.forename: Ei-ichi
authors.initials: E
authors.lastname: Miyachi
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000328:Adult; D000368:Aged; D002586:Cesium / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D015870:Gene Expression; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011743:Pyrimidines; D015222:Sodium Channels; C082246:ICI D2788; D002586:Cesium; D013779:Tetrodotoxin; D012964:Sodium