Goldfish cones contain CB1 receptors at the synaptic terminal, selectively accumulate 3H-anandamide, and contain fatty acid amide hydrolase-immunoreactivity, and voltage-gated calcium and potassium currents are modulated by CB1 ligands (Yazulla et al., 2000; Fan & Yazulla, 2003; Glaser et al., 2005). These data suggest that a retinal mechanism may account for some of the psychophysical effects of cannabis. Here, we studied the effect of a cannabinoid agonist on cone light responses. Whole-cell patch-clamp recordings were made from cones in the isolated goldfish retina. Cones were stimulated with a spot of light of variable wavelength and intensities in combination with voltage-and current-clamp protocols. Pharmacological manipulation was performed using the cannabinoid agonist WIN 55212-2 (10 microM). WIN had no effect on the absolute sensitivity of the cones or on the kinetics of the onset response. However, the light-offset response became faster, and the depolarizing overshoot was enhanced. Time constant of the offset response was reduced from 292 +/- 28 ms to 180 +/- 11 ms (n = 6) (P < 0.01) in the presence of WIN. Acceleration of the offset response was not affected by flash length from 200 ms to 10 s. This was found under current-clamp as well as under voltage-clamp conditions, indicating that the effect of WIN was mediated directly or indirectly by modulation of the cGMP-gated channels in the outer segment of the cones. The effects of WIN were not blocked by the CB1 antagonist SR141716A. With a train of "dark" flashes from a steady background, the photocurrent recovered toward baseline more quickly with WIN than in Control. In summary, cannabinoids speed up the dynamics of the phototransduction deactivation cascade in the cone outer segments. The functional consequence of this effect is to shorten the recovery time to the offset of bright flashes, perhaps resulting in an increase in contrast sensitivity.
The present study was undertaken to determine whether release of glutamate is capable of influencing dendritic morphology in a developing network of rat hippocampal neurons in vitro. Control cultures developed a dense network of fibers and evinced spontaneous electrical activity from the third day in vitro. Dendrites were examined in cultures maintained for 2 weeks in vitro: the experimental group grown in medium containing the glutamate receptor antagonists AP-5 and DNQX. Dendritic extensions were analyzed as a function of time (days in vitro) using a number of morphometric parameters, vis. the number of processes, the number and length of intermediate and terminal segments, as well as the total length of all segments. We found that the effect of age and treatment was most prominently reflected in the length of the terminal segments. Chronic addition of ionotropic glutamate receptor antagonists from day 2 in culture arrested all dendrite parameters at the prefunctional level. The results suggest that glutamate release is crucial for the onset of dendritic morphological development in hippocampal neurons.
Previously it was found that the amplitude of Ca currents in CA1 hippocampal neurons increases after adrenalectomy (ADX) of young adult rats. Preliminary data suggested that this effect of ADX is age-dependent. In the present study we therefore investigated the effect of ADX on Ca currents in three age groups: rats that were 1, 3, or 6 months old. It appeared that ADX of the youngest age group resulted in a selective enhancement of sustained, high threshold Ca currents. By contrast, ADX of the oldest rats enhanced only the low threshold, transient Ca current amplitude. The age dependency of the ADX-induced effects can be explained by developmental changes in Ca current properties in the adrenally intact rats with which ADX animals were compared. Data from acutely dissociated cells, which lack most of their dendrites, suggest that the ADX-induced changes of Ca current properties are at least partly targeted at currents generated in the distal dendrites. No significant changes were observed with age or after ADX for the mRNA expression of the alpha 1D Ca channel subunit, which forms the ionpore of the sustained high threshold L-type Ca channel. We can therefore presently not exclude that the altered amplitude of Ca current with age and ADX is due to changes in ion channel function rather than in the total number of these channels.
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