Weight F F, Schulman J A, Smith P A, Busis N A
Fed Proc. 1979 Jun;38(7):2084-94.
Long-lasting postsynaptic potentials (PSPs) generated by decreases in membrane conductance (permeability) have been reported in many types of neurons. We investigated the possible role of such long-lasting decreases in membrane conductance in the modulation of synaptic transmission in the sympathetic ganglion of the bullfrog. The molecular basis by which such conductance-decrease PSPs are generated was also investigated. Synaptic activation of muscarinic cholinergic receptors on these sympathetic neurons results in the generation of a slow EPSP (excitatory postsynaptic potential), which is accompanied by a decrease in membrane conductance. We found that the conventional "fast" EPSPs were increased in amplitude and duration during the iontophoretic application of methacholine, which activates the muscarinic postsynaptic receptors. A similar result was obtained when a noncholinergic conductance-decrease PSP--the late-slow EPSP--was elicited by stimulation of a separate synaptic pathway. The enhancement of fast EPSP amplitude increased the probability of postsynaptic action potential generation, thus increasing the efficacy of impulse transmission across the synapse. Stimulation of one synaptic pathway is therefore capable of increasing the efficacy of synaptic transmission in a second synaptic pathway by a postsynaptic mechanism. Furthermore, this enhancement of synaptic efficacy is long-lasting by virtue of the long duration of the slow PSP. Biochemical and electrophysiological techniques were used to investigate whether cyclic nucleotides are intracellular second messengers mediating the membrane permeability changes underlying slow-PSP generation. Stimulation of the synaptic inputs, which lead to the generation of the slow-PSPs, increased the ganglionic content of both cyclic AMP and cyclic GMP. However, electrophysiological analysis of the actions of these cyclic nucleotides and the actions of agents that affect their metabolism does not provide support for such a second messenger role for either cyclic nucleotide.
在许多类型的神经元中，已经报道了由膜电导（通透性）降低所产生的持久的突触后电位（PSP）。我们研究了这种膜电导的持久降低在牛蛙交感神经节突触传递调节中的可能作用。我们还研究了产生这种电导降低型PSP的分子基础。这些交感神经元上毒蕈碱型胆碱能受体的突触激活会导致缓慢兴奋性突触后电位（EPSP）的产生，同时伴有膜电导的降低。我们发现，在离子导入乙酰甲胆碱（激活毒蕈碱型突触后受体）期间，传统的“快速”EPSP在幅度和持续时间上都有所增加。当通过刺激一条单独的突触通路引发一种非胆碱能的电导降低型PSP（晚期缓慢EPSP）时，也得到了类似的结果。快速EPSP幅度的增强增加了突触后动作电位产生的概率，从而提高了突触处冲动传递的效率。因此，刺激一条突触通路能够通过突触后机制提高第二条突触通路中突触传递的效率。此外，由于缓慢PSP持续时间长，这种突触效能的增强是持久的。我们使用生化和电生理技术来研究环核苷酸是否是介导缓慢PSP产生所涉及的膜通透性变化的细胞内第二信使。刺激导致缓慢PSP产生的突触输入，会增加环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）在神经节中的含量。然而，对这些环核苷酸的作用以及影响其代谢的试剂的作用进行的电生理分析，并未为这两种环核苷酸的这种第二信使作用提供支持。
