EN
The aim was to clarify the effect of α2-adrenergic receptor activation on membrane potential, determine the cellular effector and the signal transduction pathway responsible for membrane potential changes. Recordings were made in slices in layer V mPFC pyramidal neurons in perforated-patch configuration at 33.8°C. Clonidine evoked a dose-dependent membrane hyperpolarisation. It was affected neither by the adenylyl cyclase inhibitor, protein kinase A inhibitor, phospholipase C inhibitor nor the protein kinase C inhibitor, but it was attenuated by the G-protein βγ-subunit inhibitor. The blocker of hyperpolarisation-activated cyclic nucleotidegated (HCN) channels abolished the hyperpolarisation and the α2-receptor antagonists reduced it. We conclude that α2-adrenergic receptor activation evokes hyperpolarisation in mPFC pyramidal neurons due to HCN channel inhibition in a membrane-delimited fashion by the Gβγ subunit released from the G-protein. Supported by NN401584638, NN301572940.