Agopyan N, Krnjević K, Leblond J
Anaesthesia Research Department, McGill University, Montréal, Québec, Canada.
EXS. 1989;57:77-87. doi: 10.1007/978-3-0348-9138-7_8.
In experiments on the hippocampus in situ (in rats under urethane), neither cyclic GMP nor H-8 (an antagonist of cyclic nucleotide-dependent kinases) had much effect on CA1/CA3 population spikes or on the excitatory action of ACh. This is further evidence against the idea that cyclic nucleotides play a major role as cholinergic second messengers. On the other hand, the results of tests with a PKC antagonist sphinganine are in keeping with some involvement of PKC in cholinergic actions. (Another PKC antagonist, H-7, proved to be a very powerful excitant, probably via disinhibition). Preliminary experiments on CA1 neurons in hippocampal slices (by single electrode voltage clamp), confirmed previous reports that carbachol depresses A- and C-type K currents, as well as inward Ca2+ currents; though the latter effect was sometimes mainly due to frequency-dependent inactivation of Ca currents. It is suggested that a single, primary muscarinic action, the acceleration of phosphinositide turnover, may account for a variety of secondary effects: on the one hand, via activation of PKC, a number of possible PKC-mediated actions, such as block of the slow AHP; on the other, via IP3 formation, a block of IM and a rise in cycloplasmic free Ca2+ that may cause inactivation of both Ca2(+)-inward currents, and Ca2(+)-dependent GKs.
在对海马体进行的原位实验（在乌拉坦麻醉的大鼠中）中，环磷酸鸟苷（cGMP）和H - 8（一种环核苷酸依赖性激酶的拮抗剂）对CA1/CA3群体峰电位或乙酰胆碱（ACh）的兴奋作用均无太大影响。这进一步证明了环核苷酸作为胆碱能第二信使起主要作用这一观点是错误的。另一方面，使用蛋白激酶C（PKC）拮抗剂鞘氨醇的测试结果表明PKC在胆碱能作用中有所参与。（另一种PKC拮抗剂H - 7被证明是一种非常强效的兴奋剂，可能是通过去抑制作用）。在海马切片中对CA1神经元进行的初步实验（通过单电极电压钳）证实了先前的报道，即卡巴胆碱会抑制A 型和C型钾电流以及内向钙电流；尽管后者的效应有时主要是由于钙电流的频率依赖性失活。有人提出，单一的主要毒蕈碱作用，即磷脂酰肌醇周转率的加速，可能解释了多种继发效应：一方面，通过激活PKC，产生许多可能由PKC介导的作用，如阻断缓慢的后超极化电位（AHP）；另一方面，通过肌醇三磷酸（IP3）的形成，阻断内向电流（IM）并使细胞质游离钙升高，这可能导致钙内向电流和钙依赖性钾通道（GK）失活。
