53 research outputs found
A Positive Feedback Synapse from Retinal Horizontal Cells to Cone Photoreceptors
Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that
underlies lateral inhibition and establishes the antagonistic center-surround
organization of the visual system. Cones transmit to HCs through an excitatory
synapse and HCs feed back to cones through an inhibitory synapse. Here we report
that HCs also transmit to cone terminals a positive feedback signal that
elevates intracellular Ca2+ and accelerates neurotransmitter
release. Positive and negative feedback are both initiated by AMPA receptors on
HCs, but positive feedback appears to be mediated by a change in HC
Ca2+, whereas negative feedback is mediated by a change in
HC membrane potential. Local uncaging of AMPA receptor agonists suggests that
positive feedback is spatially constrained to active HC-cone synapses, whereas
the negative feedback signal spreads through HCs to affect release from
surrounding cones. By locally offsetting the effects of negative feedback,
positive feedback may amplify photoreceptor synaptic release without sacrificing
HC-mediated contrast enhancement
Metabotropic GABA receptors facilitate L-type and inhibit N-type calcium channels in single salamander retinal neurons
Whole-cell voltage clamp experiments were performed on isolated spiking retinal neurons from the salamander retina. Calcium channel currents were studied using barium as the charge carrier while potassium and sodium currents were suppressed with TEA and TTX, respectively.Baclofen, a metabotropic GABA receptor agonist, both enhanced and suppressed high-voltage-activated calcium channel current. Baclofen facilitated an L-type channel current, and this effect was not voltage dependent. As reported previously, baclofen inhibited an N-type channel current and this action was voltage dependent.While the suppressive effect was mediated by a fast-acting, direct G-protein action, the facilitatory effect was slower and was blocked by inhibitors of protein kinase C (PKC), either GF-109203x or the PKC (19-36) sequence fragment.The pharmacology of the inhibitory and facilitatory responses differed. Commonly used antagonists of metabotropic GABA receptors, CGP35348 and CGP55845, were more potent antagonists of the inhibitory response. Similarly, a selective agonist at the metabotropic GABA receptor, APMPA, was also more effective in eliciting the inhibitory response.These observations indicate that there may be two baclofen-sensitive metabotropic GABA receptors with opposing effects on calcium channel current. This is the first description of a facilitatory action of GABAB receptors and indicates that GABA may not function exclusively as an inhibitory transmitter
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