Journal of neurochemistry
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Journal of neurochemistry · Jul 2008
Adenosine A1 receptors inhibit GABAergic transmission in rat tuberomammillary nucleus neurons.
The 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. ⋯ 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.