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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines
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Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines

机译：酸敏感离子通道1a是突触后质子受体，可影响树突棘的密度

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Extracellular proton concentrations in the brain may be an important-signal for neuron function. Proton concentrations change both acutely when synaptic vesicles release their acidic contents into the synaptic cleft and chronically during ischemia and seizures. However, the brain receptors that detect protons and their physiologic importance remain uncertain. Using organotypic hippocampal slices and biolistic transfection, we found the acid-sensing ion channel 1a (ASIC1a), localized in dendritic spines where it functioned as a proton receptor. ASIC1a also affected the density of spines, the postsynaptic site of most excitatory synapses. Decreasing ASIC1a reduced the number of spines, whereas overexpressing ASIC1a had the opposite effect. Ca2+-mediated Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling was probably responsible, because acid evoked an ASIC1a-dependent elevation of spine intracellular Ca2+ concentration, and reducing or increasing ASIC1a levels caused parallel changes in CaMKII phosphorylation in vivo. Moreover, inhibiting CaMKII prevented ASIC1a from increasing spine density. These data indicate that ASIC1a functions as a postsynaptic proton receptor that influences intracellular Ca2+ concentration and CaMKII phosphorylation and thereby the density of dendritic spines. The results provide insight into how protons influence brain function and how they may contribute to pathophysiology.
机译：大脑中的细胞外质子浓度可能是神经元功能的重要信号。当突触小泡释放酸性成分进入突触裂隙时，质子浓度急剧变化，在缺血和癫痫发作期间质子浓度变化缓慢。但是，检测质子的大脑受体及其生理重要性仍然不确定。使用器官型海马切片和生物枪法转染，我们发现了酸感应离子通道1a（ASIC1a），位于树突棘中，在其中它充当质子受体。 ASIC1a还影响棘突的密度，棘突是大多数兴奋性突触的突触后位点。降低ASIC1a会减少刺的数量，而过度表达ASIC1a会产生相反的效果。 Ca2 +介导的Ca2 + /钙调蛋白依赖性蛋白激酶II（CaMKII）信号可能是负责任的，因为酸引起了脊柱细胞内Ca2 +浓度的ASIC1a依赖性升高，并且降低或增加ASIC1a的水平导致体内CaMKII磷酸化水平的平行变化。此外，抑制CaMKII可以防止ASIC1a增加脊柱密度。这些数据表明ASIC1a充当突触后质子受体，影响细胞内Ca2 +浓度和CaMKII磷酸化，进而影响树突棘的密度。这些结果提供了质子如何影响脑功能以及它们如何有助于病理生理的见解。

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