• Do-Seop Yum, Jin-Hwa Cho, In-Sun Choi, Michiko Nakamura, Jong-Ju Lee, Maan-Gee Lee, Byung-Ju Choi, Jae-Kap Choi, and Il-Sung Jang.
• Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
• J. Neurochem. 2008 Jul 1;106(1):361-71.

AbstractThe adenosinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) was investigated in mechanically dissociated rat tuberomammillary nucleus (TMN) neurons using a conventional whole-cell patch clamp technique. Adenosine (100 microM) reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that adenosine acts presynaptically to decrease the probability of spontaneous GABA release. The adenosine action on GABAergic mIPSC frequency was completely blocked by 1 microM DPCPX, a selective A(1) receptor antagonist, and mimicked by 1 microM CPA, a selective A(1) receptor agonist. This suggests that presynaptic A(1) receptors were responsible for the adenosine-mediated inhibition of GABAergic mIPSC frequency. CPA still decreased GABAergic mIPSC frequency even either in the presence of 200 microM Cd(2+), a general voltage-dependent Ca(2+) channel blocker, or in the Ca(2+)-free external solution. However, the inhibitory effect of CPA on GABAergic mIPSC frequency was completely occluded by 1 mM Ba(2+), a G-protein coupled inwardly rectifying K(+) (GIRK) channel blocker. In addition, the CPA-induced decrease in mIPSC frequency was completely occluded by either 100 microM SQ22536, an adenylyl cyclase (AC) inhibitor, or 1 muM KT5720, a specific protein kinase A (PKA) inhibitor. The results suggest that the activation of presynaptic A(1) receptors decreases spontaneous GABAergic transmission onto TMN neurons via the modulation of GIRK channels as well as the AC/cAMP/PKA signal transduction pathway. This adenosine A(1) receptor-mediated modulation of GABAergic transmission onto TMN neurons may play an important role in the fine modulation of the excitability of TMN histaminergic neurons as well as the regulation of sleep-wakefulness.

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