title: Processing of retinal signals in normal and HCN deficient mice.
abstract: This study investigates the role of two different HCN channel isoforms in the light response of the outer retina. Taking advantage of HCN-deficient mice models and of in vitro (patch-clamp) and in vivo (ERG) recordings of retinal activity we show that HCN1 and HCN2 channels are expressed at distinct retinal sites and serve different functions. Specifically, HCN1 operate mainly at the level of the photoreceptor inner segment from where, together with other voltage sensitive channels, they control the time course of the response to bright light. Conversely, HCN2 channels are mainly expressed on the dendrites of bipolar cells and affect the response to dim lights. Single cell recordings in HCN1⁻/⁻ mice or during a pharmacological blockade of I(h) show that, contrary to previous reports, I(kx) alone is able to generate the fast initial transient in the rod bright flash response. Here we demonstrate that the relative contribution of I(h) and I(kx) to the rods' temporal tuning depends on the membrane potential. This is the first instance in which the light response of normal and HCN1- or HCN2-deficient mice is analyzed in single cells in retinal slice preparations and in integrated full field ERG responses from intact animals. This comparison reveals a high degree of correlation between single cell current clamp data and ERG measurements. A novel picture emerges showing that the temporal profile of the visual response to dim and bright luminance changes is separately determined by the coordinated gating of distinct voltage dependent conductances in photoreceptors and bipolar cells.
authors.affiliation: Department of Physiological Science, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Della Santina
authors.forename: Ilaria
authors.initials: I
authors.lastname: Piano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cangiano
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Luigi
authors.initials: L
authors.lastname: Cervetto
authors.forename: Claudia
authors.initials: C
authors.lastname: Gargini
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism*; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008027:Light; D008297:Male; D008564:Membrane Potentials / Q000528:radiation effects; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578666:Hcn1 protein, mouse; C578711:Hcn2 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels