A mechanism for nerve cell excitation by norepinephrine via α-1 adrenoceptors: inhibition of potassium M-current

Cell Mol Neurobiol. 2013 Jan;33(1):1-4. doi: 10.1007/s10571-012-9870-y. Epub 2012 Aug 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists / pharmacology
  • Animals
  • Cells, Cultured
  • Ganglia, Sympathetic / drug effects
  • Ganglia, Sympathetic / physiology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Norepinephrine / physiology*
  • Phenylephrine / pharmacology
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors*
  • Potassium Channels, Voltage-Gated / physiology*
  • Rats
  • Receptors, Adrenergic, alpha-1 / physiology*

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Receptors, Adrenergic, alpha-1
  • Phenylephrine
  • Norepinephrine