Involvement of hyperpolarization-activated cation channels in synaptic modulation.

The frequency of miniature excitatory postsynaptic currents (mEPSCs) in cultured hippocampal neurons increases under the action of drugs that trigger a rise in the intracellular concentration of cyclicAMP. It is generally believed that this type of effect is mediated by protein kinase A. Here, we show that it largely depends on the activation of hyperpolarization-activated cation channels (Ih) by cyclicAMP. In mammals, Ih channels control membrane excitability, thanks to their function as ionic channels. Here, we show that the effect of Ih channels on glutamate release is not mediated by the depolarization induced by their activation and thus is not linked to the ionic channel aspect of Ih channels. This suggests that the Ih channel could be a bifunctional protein.