Agnati L F, Bjelke B, Fuxe K
Department of Human Physiology, University of Modena, Italy.
Med Res Rev. 1995 Jan;15(1):33-45. doi: 10.1002/med.2610150104.
A volume transmission mode of communication in brain was implicit already in the early work of Golgi, who postulated the existence of electrical signals in the extracellular fluid (ECF) based on Volta's "wet conductor" made by solutions. The term volume transmission is taken from the term volume conduction describing the flow of ionic currents in the ECF as a basis for the electrocorticogram. The slow VT mode includes also chemical signals and is opposed to the fast synaptic (wiring) transmission. Every neuron may function in a dual mode, the synaptic and the volume transmission mode, when considering the autocrine and synaptic classes of communication. The paracrine- and neuroendocrine-like classes only involve the VT mode in the latter case including the CSF as a route. The chemical signals for VT are the neuropeptides, but also the classical transmitters, the monoamines, acetylcholine, GABA, and glutamate can participate, when they operate via slow, high affinity G protein coupled receptors. Ions such as K+, Ca++, and H+ also function as VT signals. The hypothesis is also introduced that CO2 can act as a multifacit long-distance VT and WT regulator besides being part of the CO2/HCO3 buffer. CO2 via regulating NMDA receptor sensitivity can also regulate NO formation, which represents a paracrine and fast VT signal. The therapy of CNS disorders is also discussed in the frame of the wiring and VT concept. Two therapeutical approaches can therefore be developed, one based on increasing WT and one based on increasing VT. In contrast to the WT therapy, which must preserve the electrotemporal code, the VT therapy can operate also with postsynaptic agonists. Therefore, a therapeutic effect with such a drug indicates that the deficiency in the communication process operates via VT. In view of the lack of very effective negative feedbacks in VT vs. WT, VT therapy may produce less tolerance and drug dependency.
大脑中的容积传递通信模式在高尔基早期的研究中就已隐含，他基于伏特用溶液制成的“湿导体”，推测细胞外液（ECF）中存在电信号。容积传递这一术语源自容积传导，容积传导描述了ECF中离子电流的流动，是脑电图的基础。缓慢的容积传递模式还包括化学信号，与快速的突触（线路）传递相对。当考虑自分泌和突触通信类别时，每个神经元都可以在突触和容积传递两种模式下发挥作用。在后一种情况下，旁分泌和神经内分泌样类别仅涉及容积传递模式，包括脑脊液作为一条途径。容积传递的化学信号是神经肽，但经典递质、单胺、乙酰胆碱、γ-氨基丁酸和谷氨酸在通过缓慢、高亲和力的G蛋白偶联受体起作用时也可以参与。钾离子、钙离子和氢离子等离子也作为容积传递信号发挥作用。还提出了一个假说，即二氧化碳除了作为二氧化碳/碳酸氢盐缓冲液的一部分外，还可以作为一种多方面的长距离容积传递和线路传递调节剂。二氧化碳通过调节NMDA受体敏感性，还可以调节一氧化氮的形成，一氧化氮代表一种旁分泌和快速容积传递信号。中枢神经系统疾病的治疗也在线路传递和容积传递概念的框架内进行了讨论。因此可以开发两种治疗方法，一种基于增强线路传递，另一种基于增强容积传递。与必须保留电时码的线路传递治疗不同，容积传递治疗也可以使用突触后激动剂。因此，用这种药物产生的治疗效果表明，通信过程中的缺陷是通过容积传递起作用的。鉴于与线路传递相比，容积传递缺乏非常有效的负反馈，容积传递治疗可能产生较少的耐受性和药物依赖性。
