α2A adrenoceptor-mediated presynaptic inhibition of GABAergic transmission in rat tuberomammillary nucleus neurons

Authors

  • Michiko Nakamura,

    1. Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea
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  • Kyungho Suk,

    1. Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
    2. Brain Science & Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
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  • Maan-Gee Lee,

    1. Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
    2. Brain Science & Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
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  • Il-Sung Jang

    Corresponding author
    1. Brain Science & Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
    • Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea
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Address correspondence and reprint requests to Il-Sung Jang, PhD, Department of Pharmacology, School of Dentistry, Kyungpook National University, 188-1, Samduk 2 ga-dong, Jung-gu, Daegu 700-412, Republic of Korea. E-mail: jis7619@mail.knu.ac.kr

Abstract

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 Ca2+ 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 Ca2+ 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.

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