Mechanisms of neuromodulation as dissected using Sr2+ at motor nerve endings.

Mechanisms of neuromodulation as dissected using Sr2+ at motor nerve endings.
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使用 Sr2 在运动神经末梢剖析神经调节机制。

DOI:
10.1152/jn.90258.2008
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发表时间:
2008
影响因子:
2.5
通讯作者:
Silinsky,EugeneM
Silinsky,EugeneM
中科院分区:
医学3区
文献类型:
--
作者:
Searl,TimothyJ;Silinsky,EugeneM

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使用二项分析作为确定神经调节剂作用部位的工具可能会因释放概率的不均匀性而复杂化。释放概率不均匀的一个潜在来源是多种形式的突触蛋白的存在,突触蛋白是ca2 +传感器,负责触发水疱胞外分泌。在这项研究中,我们使用了sr2 +,一种作用可能仅限于突触tagmins亚群的离子,试图获得二项参数p(乙酰胆碱[Ach]释放的概率)和n(乙酰胆碱量子的即时可用储存量,其中m= np)的有意义的估计。与ca2 +溶液的结果相反,Sr 2+依赖性释放的二项分析显示n对细胞外Sr 2+浓度的依赖性显著降低。在Sr -2 +溶液中,3,4 -二氨基吡啶阻断钾通道增加m,只增加p,而磷酯处理仅通过对n的影响增加m。环磷酸腺苷(cAMP)类似物CPT-cAMP增加m,同时增加n和p。CPT-cAMP对p的作用不影响n,但对p的作用被蛋白激酶A (PKA)抑制剂阻断,而对n的作用被8-CPT-2 ' -O-Me-cAMP模拟。直接被cAMP激活的交换蛋白的选择性激动剂,也被称为cAMP敏感的鸟嘌呤核苷酸交换蛋白。研究结果证明了sr2 +溶液中二项分布的效用,以及环AMP对两栖动物神经肌肉连接处pka依赖性和pka非依赖性过程的双重影响。
The use of binomial analysis as a tool for determining the sites of action of neuromodulators may be complicated by the nonuniformity of release probability. One of the potential sources for nonuniformity of release probability is the presence of multiple forms of synaptotagmins, the Ca 2+ sensors responsible for triggering vesicular exocytosis. In this study we have used Sr 2+, an ion whose actions may be restricted to a subpopulation of synaptotagmins, in an attempt to obtain meaningful estimates of the binomial parameters p (the probability of evoked acetylcholine [Ach] release) and n (the immediate available store of ACh quanta, whereby m= np). In contrast to results in Ca 2+ solutions, binomial analysis of Sr 2+-dependent release reveals a dramatically reduced dependence of n on extracellular Sr 2+ concentrations. In Sr 2+ solutions, blockade of potassium channels with 3, 4-diaminopyridine increased m by an exclusive increase in p, whereas treatment with phorbol ester increased m solely by effects on n. The cyclic adenosine monophosphate (cAMP) analogue CPT-cAMP increased m by increasing both n and p. The effect of CPT-cAMP on p but not on n was blocked by protein kinase A (PKA) inhibitors, whereas the effect on n was mimicked by 8-CPT-2′-O-Me-cAMP, a selective agonist for exchange protein directly activated by cAMP, otherwise known as the cAMP-sensitive guanine nucleotide-exchange protein. The results demonstrate both the utility of the binomial distribution in Sr 2+ solutions and the dual effects of cyclic AMP on both PKA-dependent and PKA-independent processes at the amphibian neuromuscular junction.
DOI: 10.1113/jphysiol.1981.sp013586
发表时间: 1981-01-01
影响因子: 5.5
作者:
MCLACHLAN, EM;MARTIN, AR
通讯作者: MARTIN, AR
DOI: 10.2307/2529338
发表时间: 1976
期刊: Biometrics
影响因子: 1.9
作者:
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DOI: 10.1023/a:1015104105262
发表时间: 2001-12-01
影响因子: 4
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DOI: 10.1113/jphysiol.1975.sp010939
发表时间: 1975-01-01
影响因子: 5.5
作者:
BENNETT, MR;FLORIN, T;HALL, R
通讯作者: HALL, R
3,4-二氨基吡啶对青蛙神经肌肉接头乙酰胆碱释放的影响。
DOI: 10.1016/0014-2999(80)90499-9
发表时间: 1980
影响因子: 5
作者:
N. Durant;I. Marshall
通讯作者: I. Marshall