Neuroscience
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The ionotropic GABA(C) receptor, formed by GABA rho subunits, is known to be modulated by a variety of endogenous compounds, as well as by changes in pH. In this study, we explore the proton sensitivity of the GABA rho subunits cloned from the perch retina, and report a novel action of high pH on the homomeric receptor formed by one of the GABA rho subunits, the perch-rho(1B) subunit. Raising extracellular pH to 9.5 significantly accelerated GABA deactivation responses elicited from oocytes expressing the perch-rho(1B) subunit, and reduced its sensitivity to GABA. ⋯ When considered in terms of a model describing the activation of GABA(C) receptors, in which pH can potentially affect either the binding affinity or the rate of channel closure, the results were consistent with the view that external alkalization reduces the gating efficiency of the receptor. To identify the proton sensitive domain(s) of the perch-rho(1B) receptor, chimeras were constructed by domain swapping with other perch-rho subunits. Analysis of the pH sensitivities of the various chimeric receptors revealed that the alkaline-sensitive residues are located in the N-terminal region of the perch-rho(1B) subunit.
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Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. ⋯ Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina.
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Sex-related differences in the sensitivity to pain and in the response to analgesics have been reported including higher perceptual responses to experimentally induced pain and the higher prevalence of many pain syndromes in women compared with men. This study examines whether alpha2-adrenoceptor-mediated antinociceptive effects are reduced by estrogen which could account for the sex-related differences in pain perception and modulation. Clonidine, an alpha2-adrenoceptor agonist, has been shown to inhibit noxious stimulus-evoked nociceptive behavior as well as the responses of nociceptive neurons in the medullary dorsal horn. ⋯ Finally, the effect of clonidine was reversed by yohimbine, an alpha2-adrenoceptor antagonist, in male and OVX groups on thermal nociceptive test. These results lead us to conclude that activation of alpha2-adrenoceptors produces sex-specific, estrogen dependent modulation of nociception in the trigeminal region of the rat. A decreased alpha2-adrenoceptor-mediated inhibition could be one of the factors responsible for the higher prevalence of pain syndromes in females.
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Members of various transport protein families including ATP-binding cassette transporters and solute carriers were shown to be expressed in brain capillaries, choroid plexus, astrocytes or neurons, controlling drug and metabolite distribution to and from the brain. However, data are currently very limited on how the expression of these transport systems is affected by damage to the brain such as stroke. Therefore we studied the expression of four selected transporters, P-glycoprotein (Mdr1a/b; Abcb1a/b), Mrp5 (Abcc5), Bcrp (Abcg2), and Oatp2 (Slc21a5) in a rat model for stroke. ⋯ For Mrp5, an up-regulation was observed in neurons in the periinfarcted region (day 14). In conclusion, after stroke the transport proteins were up-regulated with a maximum at day 14, a time point that coincides with behavioral recuperation. The study further suggests Bcrp as a pronounced marker for the regenerative process and a possible functional role of Mrp5 in surviving neurons.