Wang Xin, Evans Cory, Mendelowitz David
Department of Pharmacology, George Washington University, 2300 Eye Street NW, Washington, DC 20037, USA.
Neuropharmacology. 2004 Mar;46(3):372-8. doi: 10.1016/j.neuropharm.2003.09.013.
Previous work has shown endogenous cholinergic activity facilitates both GABAergic and glycinergic neurotransmission to premotor cardiac vagal neurons. Exogenous application of nicotine increases the frequency of glycinergic and GABAergic inhibitory postsynaptic currents (IPSCs) and miniature IPSCs (mIPSCs) to cardiac vagal neurons. In this study we examined whether the nicotine evoked facilitation of GABAergic and glycinergic neurotransmission to cardiac vagal neurons is dependent or independent of activation of voltage dependent calcium channels. Nicotine evoked increases in GABAergic and glycinergic mIPSCs in cardiac vagal neurons which were blocked by the non-specific calcium channel antagonist cadmium (100 microM). Application of the L (Cav 1) type calcium channel antagonist nimodipine (10 microM) had no effect. However, the increase in both GABAergic and glycinergic mIPSCs elicited by nicotine was abolished by the P/Q (Cav 2.1) voltage gated calcium channel antagonist omega-agatoxin IVA (100 nM). Omega-conotoxin GVIA (1 microM), a specific blocker of N (Cav 2.2) type voltage gated calcium currents, inhibited the nicotine elicited augmentation of GABA and abolished the increase in glycine mIPSC frequency. This work demonstrates that the nicotine evoked facilitation of GABAergic and glycinergic neurotransmission to cardiac vagal neurons is dependent upon activation of P/Q (Cav 2.1) and N (Cav 2.2) type calcium channels.
先前的研究表明，内源性胆碱能活性可促进向运动前心脏迷走神经元的γ-氨基丁酸能和甘氨酸能神经传递。外源性应用尼古丁可增加向心脏迷走神经元的甘氨酸能和γ-氨基丁酸能抑制性突触后电流（IPSCs）以及微小IPSCs（mIPSCs）的频率。在本研究中，我们检测了尼古丁诱发的向心脏迷走神经元的γ-氨基丁酸能和甘氨酸能神经传递促进作用是否依赖或不依赖于电压依赖性钙通道的激活。尼古丁诱发心脏迷走神经元中γ-氨基丁酸能和甘氨酸能mIPSCs增加，这被非特异性钙通道拮抗剂镉（100微摩尔）阻断。应用L（Cav 1）型钙通道拮抗剂尼莫地平（10微摩尔）没有效果。然而，尼古丁诱发的γ-氨基丁酸能和甘氨酸能mIPSCs增加被P/Q（Cav 2.1）电压门控钙通道拮抗剂ω-芋螺毒素IVA（100纳摩尔）消除。ω-芋螺毒素GVIA（1微摩尔），一种N（Cav 2.2）型电压门控钙电流的特异性阻滞剂，抑制了尼古丁诱发的γ-氨基丁酸增加，并消除了甘氨酸mIPSC频率的增加。这项工作表明，尼古丁诱发的向心脏迷走神经元的γ-氨基丁酸能和甘氨酸能神经传递促进作用依赖于P/Q（Cav 2.1）和N（Cav 2.2）型钙通道的激活。
