Mondragão Miguel A, Schmidt Hartmut, Kleinhans Christian, Langer Julia, Kafitz Karl W, Rose Christine R
Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, Leipzig, Germany.
J Physiol. 2016 Oct 1;594(19):5507-27. doi: 10.1113/JP272431. Epub 2016 May 27.
Neuronal activity causes local or global sodium signalling in neurons, depending on the pattern of synaptic activity. Recovery from global sodium loads critically relies on Na(+) /K(+) -ATPase and an intact energy metabolism in both somata and dendrites. For recovery from local sodium loads in dendrites, Na(+) /K(+) -ATPase activity is not required per se. Instead, recovery is predominately mediated by lateral diffusion, exhibiting rates that are 10-fold higher than for global sodium signals. Recovery from local dendritic sodium increases is still efficient during short periods of energy deprivation, indicating that fast diffusion of sodium to non-stimulated regions strongly reduces local energy requirements.
Excitatory activity is accompanied by sodium influx into neurones as a result of the opening of voltage- and ligand-activated channels. Recovery from resulting sodium transients has mainly been attributed to Na(+) /K(+) -ATPase (NKA). Because sodium ions are highly mobile, diffusion could provide an additional pathway. We tested this in hippocampal neurones using whole-cell patch-clamp recordings and sodium imaging. Somatic sodium transients induced by local glutamate application recovered at a maximum rate of 8 mm min(-1) (∼0.03 mm min(-1 ) μm(-2) ). Somatic sodium extrusion was accelerated at higher temperature and blocked by ouabain, emphasizing its dependence on NKA. Moreover, it was slowed down during inhibition of glycolysis by sodium fluoride (NaF). Local glutamate application to dendrites revealed a 10-fold higher apparent dendritic sodium extrusion rate compared to somata. Recovery was almost unaltered by increased temperature, ouabain or NaF. We found that sodium diffused along primary dendrites with a diffusion coefficient of ∼330 μm²/s. During global glutamate application, impeding substantial net diffusion, apparent dendritic extrusion rates were reduced to somatic rates and also affected by NaF. Numerical simulations confirmed the essential role of NKA for the recovery of somatic, but not dendritic sodium loads. Our data show that sodium export upon global sodium increases is largely mediated by NKA and depends on an intact energy metabolism. For recovery from local dendritic sodium increases, diffusion dominates over extrusion, operating efficiently even during short periods of energy deprivation. Although sodium will eventually be extruded by the NKA, its diffusion-based fast dissemination to non-stimulated regions might reduce local energy requirements.
神经元活动会导致神经元内局部或整体的钠信号传导，这取决于突触活动的模式。从整体钠负荷中恢复关键依赖于钠钾ATP酶以及胞体和树突中完整的能量代谢。对于树突中局部钠负荷的恢复，本身并不需要钠钾ATP酶的活性。相反，恢复主要由横向扩散介导，其速率比整体钠信号高10倍。在能量剥夺的短时间内，从局部树突钠增加中恢复仍然是有效的，这表明钠快速扩散到未受刺激区域会大大降低局部能量需求。
兴奋性活动伴随着由于电压门控和配体门控通道开放导致的钠离子流入神经元。从由此产生的钠瞬变中恢复主要归因于钠钾ATP酶（NKA）。由于钠离子具有高度的流动性，扩散可能提供另一条途径。我们使用全细胞膜片钳记录和钠成像在海马神经元中对此进行了测试。局部应用谷氨酸诱导的胞体钠瞬变以最大速率8 mmol·min⁻¹（约0.03 mmol·min⁻¹·μm⁻²）恢复。胞体钠的排出在较高温度下加速，并被哇巴因阻断，强调了其对NKA的依赖性。此外，在氟化钠（NaF）抑制糖酵解期间，其速度减慢。局部向树突应用谷氨酸显示，与胞体相比，树突钠排出的表观速率高10倍。温度升高、哇巴因或NaF对恢复几乎没有影响。我们发现钠沿着初级树突扩散，扩散系数约为330μm²/s。在整体应用谷氨酸期间，阻碍大量净扩散，树突的表观排出速率降低到胞体速率，并且也受NaF影响。数值模拟证实了NKA对于胞体钠负荷恢复的重要作用，但对树突钠负荷恢复并非如此。我们的数据表明，整体钠增加时的钠输出主要由NKA介导，并依赖于完整的能量代谢。对于从局部树突钠增加中恢复，扩散比排出占主导，即使在能量剥夺的短时间内也能有效运作。虽然钠最终会被NKA排出，但其基于扩散的快速扩散到未受刺激区域可能会降低局部能量需求。
