Adenosine modulates the excitability of layer II stellate neurons in entorhinal cortex through A1 receptors

Stellate neurons in layer II entorhinal cortex (EC) provide the main output from the EC to the hippocampus. It is believed that adenosine plays a crucial role in neuronal excitability and synaptic transmission in the CNS, however, the function of adenosine in the EC is still elusive. Here, the data reported showed that adenosine hyperpolarized stellate neurons in a concentration‐dependent manner, accompanied by a decrease in firing frequency. This effect corresponded to the inhibition of the hyperpolarization‐activated, cation nonselective (HCN) channels. Surprisingly, the adenosine‐induced inhibition was blocked by 3 μM 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX), a selective A₁ receptor antagonists, but not by 10 μM 3,7‐dimethyl‐1‐propargylxanthine (DMPX), a selective A₂ receptor antagonists, indicating that activation of adenosine A₁ receptors were responsible for the direct inhibition. In addition, adenosine reduced the frequency but not the amplitude of miniature EPSCs and IPSCs, suggesting that the global depression of glutamatergic and GABAergic transmission is mediated by a decrease in glutamate and GABA release, respectively. Again the presynaptic site of action was mediated by adenosine A₁ receptors. Furthermore, inhibition of spontaneous glutamate and GABA release by adenosine A₁ receptor activation was mediated by voltage‐dependent Ca²⁺ channels and extracellular Ca²⁺. Therefore, these findings revealed direct and indirect mechanisms by which activation of adenosine A₁ receptors on the cell bodies of stellate neurons and on the presynaptic terminals could regulate the excitability of these neurons. © 2010 Wiley‐Liss, Inc.