Srinivas Kalyan V, Sikdar Sujit K
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
Eur J Neurosci. 2008 Dec;28(11):2195-212. doi: 10.1111/j.1460-9568.2008.06519.x.
The cellular and molecular mechanisms that underlie acquired changes in Ca(2+) dynamics of different neuronal compartments are important in the induction and maintenance of epileptiform activity. Simultaneous electrophysiology and Ca(2+) imaging techniques were used to understand the basic properties of dendritic Ca(2+) signaling in rat subicular pyramidal neurons during epileptiform activity. Distance-dependent changes in the Ca(2+) decay kinetics locked to spontaneous epileptiform discharges and back-propagating action potentials were observed in the apical dendrites. A decrement in the mean tau value of Ca(2+) decay was observed in distal parts (95-110 mum) of the apical dendrites compared with proximal segments (30-45 mum) in in-vitro epileptic conditions but not in control. Pharmacological agents that block Ca(2+) transporters, i.e. Na(+)/ Ca(2+) exchangers (Benzamil), plasma membrane Ca(2+)-ATPase pumps (Calmidazolium) and smooth endoplasmic reticulum Ca(2+)-ATPase pumps (Thapsigargin), were applied locally to the proximal and distal part of the apical dendrites in both experimental conditions to understand the molecular aspects of the Ca(2+) extrusion mechanisms. The relative contribution of Na(+)/Ca(2+) exchangers in Ca(2+) extrusion was higher in the distal apical dendrites in the in-vitro epileptic condition and this property modulated the excitability of the neuron in simulation. The Ca(2+) homeostatic mechanisms that restore normal Ca(2+) levels could play a major neuroprotective role in the distal dendrites that receive synaptic inputs.
不同神经元区室中钙（Ca(2+)）动力学获得性变化的细胞和分子机制在癫痫样活动的诱导和维持中起着重要作用。同时使用电生理学和钙（Ca(2+)）成像技术来了解癫痫样活动期间大鼠海马下托锥体神经元树突状钙（Ca(2+)）信号传导的基本特性。在顶端树突中观察到与自发性癫痫样放电和反向传播动作电位相关的钙（Ca(2+)）衰减动力学的距离依赖性变化。在体外癫痫状态下，与近端节段（30 - 45μm）相比，顶端树突远端部分（95 - 110μm）的钙（Ca(2+)）衰减平均时间常数减小，但在对照中未观察到。在两种实验条件下，将阻断钙（Ca(2+)）转运体的药物，即钠/钙（Na(+)/Ca(2+)）交换体（苯扎明）、质膜钙（Ca(2+)）-ATP酶泵（卡咪达唑）和平滑内质网钙（Ca(2+)）-ATP酶泵（毒胡萝卜素）局部应用于顶端树突的近端和远端，以了解钙（Ca(2+)）外排机制的分子方面。在体外癫痫状态下，钠/钙（Na(+)/Ca(2+)）交换体在顶端树突远端钙（Ca(2+)）外排中的相对贡献更高，并且这种特性在模拟中调节了神经元的兴奋性。恢复正常钙（Ca(2+)）水平的钙（Ca(2+)）稳态机制可能在接受突触输入的远端树突中发挥主要的神经保护作用。
