Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
J Neurochem. 2013 Jun;125(6):832-42. doi: 10.1111/jnc.12259. Epub 2013 Apr 25.
Histaminergic neurons within the tuberomammillary nucleus (TMN) play an important role in the regulation of sleep-wakefulness. Here, we report the adrenergic modulation of GABAergic transmission in rat TMN histaminergic neurons using a conventional whole-cell patch clamp technique. Norepinephrine (NE) reversibly decreased the amplitude of action potential-dependent GABAergic inhibitory post-synaptic currents (IPSCs) and increased the paired pulse ratio. The NE-induced inhibition of GABAergic IPSCs was mimicked by clonidine, a selective α2 adrenoceptor agonist. However, cirazoline and isoproterenol, nonselective α1 and β adrenoceptor agonists, respectively, had no effect on GABAergic IPSCs. The NE-induced inhibition of GABAergic IPSCs was significantly blocked by BRL44408, a selective α2A adrenoceptor antagonist, but not imiloxan or JP1302, a selective α2B and α2C adrenoceptor antagonists. The extent of NE-induced inhibition of GABAergic IPSCs was inversely proportional to the extracellular Ca(2+) concentration. Pharmacological agents affecting the activities of adenylyl cyclase or G-protein-coupled inwardly rectifying K(+) channels did not affect the NE-induced inhibition of GABAergic IPSCs. However, NE had no effect on the frequency and amplitude of GABAergic miniature IPSCs. These results suggest that NE acts on presynaptic α2A adrenoceptor to inhibit action potential-dependent GABA release via the inhibition of Ca(2+) influx from the extracellular space to GABAergic nerve terminals, and that this α2A adrenoceptor-mediated modulation of GABAergic transmission may be involved in regulating the excitability of TMN histaminergic neurons.
位于结节乳头核（TMN）的组胺能神经元在调节睡眠-觉醒中发挥着重要作用。在这里，我们使用常规全细胞膜片钳技术报告了去甲肾上腺素（NE）对大鼠 TMN 组胺能神经元 GABA 能传递的调制。去甲肾上腺素（NE）可逆性地减小动作电位依赖性 GABA 能抑制性突触后电流（IPSCs）的幅度并增加成对脉冲比。选择性 α2 肾上腺素能受体激动剂可乐定模拟了 NE 诱导的 GABA 能 IPSC 抑制。然而，非选择性 α1 和 β 肾上腺素能受体激动剂可乐定、胍那啶和异丙肾上腺素对 GABA 能 IPSC 没有影响。选择性 α2A 肾上腺素能受体拮抗剂 BRL44408 显著阻断了 NE 诱导的 GABA 能 IPSC 抑制，但选择性 α2B 和 α2C 肾上腺素能受体拮抗剂 imiloxan 或 JP1302 没有作用。NE 诱导的 GABA 能 IPSC 抑制的程度与细胞外 Ca2+浓度成反比。影响腺苷酸环化酶或 G 蛋白偶联内向整流 K+通道活性的药物对 NE 诱导的 GABA 能 IPSC 抑制没有影响。然而，NE 对 GABA 能微小 IPSC 的频率和幅度没有影响。这些结果表明，NE 作用于突触前α2A 肾上腺素能受体，通过抑制细胞外空间的 Ca2+内流来抑制动作电位依赖性 GABA 释放，这种 α2A 肾上腺素能受体介导的 GABA 能传递调制可能参与调节 TMN 组胺能神经元的兴奋性。
