Functional characterisation and subcellular localisation of HCN1 channels in rabbit retinal rod photoreceptors

Gating of voltage-dependent conductances in retinal photoreceptors is the first step of a process leading to the enhancement of the temporal performance of the visual system. The molecular components underlying voltage-dependent gating in rods are presently poorly defined. In the present work we have investigated the isoform composition and the functional characteristics of hyperpolarisation-activated cyclic nucleotide-gated channels (HCN) in rabbit rods. Using immunocytochemistry we show the expression in the inner segment and cell body of the isoform I (HCN1). Electrophysiological investigations show that hyperpolarisation-activated currents (I-h) can be measured only from the cell regions where HCN1 is expressed. Half-activation voltage (-75.0 +/- 0.3 mV) and kinetics (t(nu2) of 101 +/- 8 ins at -110 mV and 20degreesC) of the I-h in rods are similar to those of the macroscopic current carried by homomeric rabbit HCN1 channels expressed in HEK 293 cells. The homomeric nature of HCN1 channels in rods is compatible with the observation that cAMP induces a small shift (2.3 +/- 0.8 mV) in the half-activation voltage of I-h. In addition, the observation that within the physiological range of membrane potentials, cAMP does not significantly affect the gain of the current-to-voltage conversion, may reflect the need to protect the first step in the processing of visual signals from changes in cAMP turnover

Synthesis and affinity for serotonin and dopamine transporters of some benzophenone oxime ether derivatives

In a previous study, we reported the synthesis of several 3-(methylenaminoxymethyl)-substituted piperidine derivatives and their ability to interfere with the transmission mediated by biogenic amines. The present study describes the preparation of some new oxime derivatives and their capacity to inhibit serotonin (SERT) and dopamine (DAT) transporters expressed at the level of the rabbit cortex and the striatal membranes, respectively. All the compounds showed Ki values in the micromolar range on both transporters

Analysis of pharmacologically isolated component of ERG

An harmonic analysis was applied to the electroretinogram (ERG) measured in intact cat eyes in control conditions and after pharmacological isolation of the components attributed to photoreceptors (PIII) and bipolar neurons (PII). The frequency response curves obtained in various conditions showed that the bandwidth of the PII component extends over a range of stimulus frequencies higher than the bandwidth of PIII. The enhancement of the PII response to stimuli of high temporal frequency suggests the presence of a frequency dependent gain control located either pre- and/or post-synaptically in the transmission line between the phototransductive cascade and bipolar neurons. A possible role of these processes is to enhance relevant visual information whilst selectively attenuating low frequency signals originating in the transductive cascade