Smith A B, Cunnane T C
University Department of Pharmacology, Oxford, U.K.
Neuroscience. 1996 Feb;70(3):817-24. doi: 10.1016/s0306-4522(96)83018-1.
Intracellular recording techniques were used to study neurotransmitter release in the guinea-pig isolated vas deferens. Low concentrations of the irreversible and selective N-type calcium channel blocker omega-conotoxin GVIA have previously been shown to block excitatory junction potentials evoked by low frequencies (< or = 1 Hz) of nerve stimulation. Here we report a component of action potential-evoked release which is insensitive to high concentrations of omega-conotoxin GVIA. We have termed this component "residual release" and show (i) it is positively frequency-dependent, (ii) its magnitude is dependent on both the train length and interval between trains, (iii) "residual release" can be modulated through prejunctional alpha 2-adrenoceptors and (iv) "residual release" is insensitive to many calcium entry blockers but abolished by omega-grammotoxin SIA and cadmium ions. Although noradrenaline is released by nerve action potentials, residual excitatory junction potentials were abolished by alpha,beta-methylene-ATP and therefore resulted entirely from the actions of neuronally released ATP acting through postjunctional P2x-purinoceptors. The results suggest that calcium entry through a novel, pharmacologically uncharacterized voltage-dependent calcium channel is responsible for "residual release" in sympathetic nerve terminals. It seems that in response to single or short trains of nerve action potentials, N-type calcium channels dominate the release process. However, at higher frequencies other voltage-dependent calcium channels are recruited and these may have an important role to play in triggering the mechanisms underlying frequency-dependent facilitation.
采用细胞内记录技术研究豚鼠离体输精管中的神经递质释放。先前已表明，低浓度的不可逆性和选择性N型钙通道阻滞剂ω-芋螺毒素GVIA可阻断低频（≤1Hz）神经刺激诱发的兴奋性接头电位。在此，我们报告了动作电位诱发释放的一个成分，它对高浓度的ω-芋螺毒素GVIA不敏感。我们将这个成分称为“残余释放”，并表明：（i）它呈正频率依赖性；（ii）其幅度取决于串刺激的长度和串刺激之间的间隔；（iii）“残余释放”可通过突触前α2肾上腺素能受体进行调节；（iv）“残余释放”对许多钙内流阻滞剂不敏感，但可被ω-粒毒素SIA和镉离子消除。尽管去甲肾上腺素由神经动作电位释放，但残余兴奋性接头电位可被α,β-亚甲基-ATP消除，因此完全是由神经元释放的ATP通过突触后P2x嘌呤受体发挥作用所致。结果表明，通过一种药理学特性未明确的新型电压依赖性钙通道的钙内流，是交感神经末梢“残余释放”的原因。似乎在对单个或短串神经动作电位的反应中，N型钙通道在释放过程中起主导作用。然而，在较高频率时，其他电压依赖性钙通道被启用，它们可能在触发频率依赖性易化的潜在机制中发挥重要作用。
