A Mechanism for Nerve Cell Excitation by Norepinephrine via Alpha-1 Adrenoceptors: Inhibition of Potassium M-Current

Some of the excitatory effects of norepinephrine on central neurons are mediated by alpha-1 (α1) adrenoceptors. These receptors are coupled to the Gq family of G proteins, and hence stimulate hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate. Other receptors of this type can excite neurons by inhibiting the subthreshold voltage-gated potassium M-current. We tested this possibility using rat sympathetic neurons transformed to express α1a receptors. The α1 agonist phenylephrine strongly inhibited the M-current recorded under voltage-clamp by 72 ± 11 % (n = 4) and in an unclamped neuron dramatically increased the number of action potentials produced by a 2 s depolarizing current step from 2 to 40, without effect on control neurons devoid of α1 receptors. We suggest that this might be a potential cause of the increased excitability produced by norepinephrine in some central neurons.