J Neurophysiol (March 1, 2003). 10.1152/jn.00516.2002
Submitted on Submitted 5 July 2002; accepted in final form 26 October 2002

Adenosine A₁ Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in Immature Rat Hippocampal CA1 Neurons

Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

Jeong, Hyo-Jin, Il-Sung Jang, Junichi Nabekura, and Norio Akaike. Adenosine A₁ Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in Immature Rat Hippocampal CA1 Neurons. J. Neurophysiol. 89: 1214-1222, 2003. In the mechanically dissociated rat hippocampal CA1 neurons with native presynaptic nerve endings, namely "synaptic bouton" preparation, the purinergic modulation of spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) was investigated using whole-cell recording mode under the voltage-clamp conditions. In immature neurons, adenosine (10 µM) reversibly decreased GABAergic mIPSC frequency without affecting the mean current amplitude. The inhibitory effect of adenosine transmission was completely blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), a selective A₁ receptor antagonist, and was mimicked by N⁶-cyclopentyladenosine (CPA, 1 µM), a selective A₁ receptor agonist. However, CPA had no effect on GABAergic mIPSC frequency in postnatal 30 day neurons. N-ethylmaleimide (10 µM), a guanosine 5'-triphosphate binding protein uncoupler, and Ca²⁺-free external solution removed the CPA-induced inhibition of mIPSC frequency. K⁺ channel blockers, 4-aminopyridine (100 µM) and Ba²⁺ (1 mM), had no effect on the inhibitory effect of CPA on GABAergic mIPSC frequency. Stimulation of adenylyl cyclase with forskolin (10 µM) prevented the CPA action on GABAergic mIPSC frequency. Rp-cAMPS (100 µM), a selective PKA inhibitor, also blocked the CPA action. It was concluded that the activation of presynaptic A₁ receptors modulates the probability of spontaneous GABA release via cAMP- and protein kinase A dependent pathway. This A₁ receptor-mediated modulation of GABAergic transmission may play an important role in the regulation of excitability of immature hippocampal CA1 neurons.