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Channel opening by anesthetics and GABA induces similar changes in the GABAA receptor M2 segment 总被引:1,自引:0,他引:1
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For many general anesthetics, their molecular basis of action involves interactions with GABA(A) receptors. Anesthetics produce concentration-dependent effects on GABA(A) receptors. Low concentrations potentiate submaximal GABA-induced currents. Higher concentrations directly activate the receptors. Functional effects of anesthetics have been characterized, but little is known about the conformational changes they induce. We probed anesthetic-induced conformational changes in the M2 membrane-spanning, channel-lining segment using disulfide trapping between engineered cysteines. Previously, we showed that oxidation by copper phenanthroline in the presence of GABA of the M2 6' cysteine mutants, alpha(1)T261Cbeta(1)T256C and alpha(1)beta(1)T256C resulted in formation of an intersubunit disulfide bond between the adjacent beta-subunits that significantly increased the channels' spontaneous open probability. Oxidation in GABA's absence had no effect. We examined the effect on alpha(1)T261Cbeta(1)T256C and on alpha(1)beta(1)T256C of oxidation by copper phenanthroline in the presence of potentiating and directly activating concentrations of the general anesthetics propofol, pentobarbital, and isoflurane. Oxidation in the presence of potentiating concentration of anesthetics had little effect. Oxidation in the presence of directly activating anesthetic concentrations significantly increased the channels' spontaneous open probability. We infer that activation by anesthetics and GABA induces a similar conformational change at the M2 segment 6' position that is related to channel opening. 相似文献
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During 2004, four experiments were carried out, one each season, in order to determine the species composition and seasonal dynamics of Calliphoridae in a rural area of Córdoba (Argentina). Two pigs (Sus scrofa L.), weighing approximately 8 Kg each, were used in each experiment. They were killed with a blow to the head and immediately placed in a variant of the Schoenly et al. (1991) trap. One pig was exposed in the shade and the other one under direct sunlight. The insect fauna was collected daily during the four first weeks and every two or three days thereafter. A total of 16.609 adults of Calliphoridae were collected, and later on identified as one of the following seven species: Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), Phaenicia sericata (Meigen), Phaenicia eximia (Wiedemann), Cochliomyia macellaria (Fabricius), Sarconesia chlorogaster (Wiedemann) and Calliphora vicina Robineau-Desvoidy. C. albiceps was the dominant species in summer, autumn and spring, being replaced in winter by C. vicina, S. chlorogaster and P. sericata. The analysis of the seasonal distribution of the species revealed that the greater incidences are in the months of summer, autumn and spring. 相似文献
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The alpha7 subtype of the neuronal nicotinic acetylcholine receptors (nAChRs) was targeted for the design of selective agonists deriving from the quinuclidine scaffold. Arylidene groups at the 3-position and N-methyl quinuclidine were found to be selective agonists with EC(50)s of 1.5 and 40 microM, respectively. 相似文献
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Sidney Horenstein 《Evolution》2011,4(3):546-553
A review of recent media publications and journals containing articles about evolution and paleontology. 相似文献
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