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.

Processing of Retinal Signals in Normal and HCN Deficient Mice

DELLA SANTINA, LUCA
Primo
;
PIANO, ILARIA
Co-primo
;
CANGIANO, LORENZO
Co-primo
;
CAPUTO, ANTONELLA;CERVETTO, LUIGI;GARGINI, MARIA CLAUDIA
2012-01-01

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.
2012
DELLA SANTINA, Luca; Piano, Ilaria; Cangiano, Lorenzo; Caputo, Antonella; Ludwig, A; Cervetto, Luigi; Gargini, MARIA CLAUDIA
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/188560
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