title: A mechanism for nerve cell excitation by norepinephrine via α-1 adrenoceptors: inhibition of potassium M-current.
abstract: 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.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Filippov
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D009638:Norepinephrine