Light responses in the mouse retina are prolonged upon targeted deletion of the HCN1 channel gene.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels contribute to pacemaker activity, and co-determine the integrative behaviour of neurons and shape their response to synaptic stimulation. Four channel isoforms, HCN1-4, have been described in mammals. Recent studies showed particularly strong expression of HCN1 channels in rods and cones of the rat retina, suggesting that HCN1 channels are involved in the shaping of light responses in both types of photoreceptors. Therefore, the loss of HCN1 channels should lead to pronounced changes in light-induced electrical responses under both scotopic and photopic conditions. This was tested using a mouse transgenic approach. We used immunohistochemistry and patch-clamp recording to study the distribution of HCN1 channels in the mouse retina. HCN1 channels were strongly expressed in rod and cone photoreceptors, as well as in some bipolar, amacrine and ganglion cell types. In electroretinograms (ERGs) from animals in which the HCN1 channel gene had been knocked out, the b-wave amplitudes were unaltered (scotopic conditions) or somewhat reduced (photopic conditions), whereas the duration of both scotopic and photopic ERG responses was strikingly prolonged. Our data suggest that in visual information processing, shortening and shaping of light responses by activation of HCN1 at the level of the photoreceptors is an important step in both scotopic and photopic pathways.
Knop
Gabriel C
GC
Institut für Neurowissenschaften und Biophysik, Forschungszentrum Jülich, Leo-Brandt-Strasse, D-52425 Jülich, Germany.
Seeliger
Mathias W
MW
Thiel
Frank
F
Mataruga
Anja
A
Kaupp
U Benjamin
UB
Friedburg
Christoph
C
Tanimoto
Naoyuki
N
Müller
Frank
F
D025042:Amacrine Cells / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D004596:Electroretinography; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000528:radiation effects*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000528:radiation effects; D015221:Potassium Channels / Q000235:genetics*; D012160:Retina / Q000378:metabolism* / Q000528:radiation effects*; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000528:radiation effects; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000528:radiation effects; D009435:Synaptic Transmission / Q000235:genetics / Q000528:radiation effects; D014785:Vision, Ocular / Q000235:genetics*
D054815:Cyclic Nucleotide-Gated Cation Channels; C578666:Hcn1 protein, mouse; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels