G protein alpha subunit G alpha z couples neurotransmitter receptors to ion channels in sympathetic neurons

Neuron. 1998 Nov;21(5):1201-12. doi: 10.1016/s0896-6273(00)80636-4.


The functional roles subserved by G(alpha)z, a G protein alpha subunit found predominantly in neuronal tissues, have remained largely undefined. Here, we report that G(alpha)z coupled neurotransmitter receptors to N-type Ca2+ channels when transiently overexpressed in rat sympathetic neurons. The G(alpha)z-mediated inhibition was voltage dependent and PTX insensitive. Recovery from G(alpha)z-mediated inhibition was extremely slow but accelerated by coexpression with RGS proteins. G(alpha)z selectively interacted with a subset of receptors that ordinarily couple to N-type Ca2+ channels via PTX-sensitive Go/i proteins. In addition, G(alpha)z rescued the activation of heterologously expressed GIRK channels in PTX-treated neurons. These results suggest that G(alpha)z is capable of coupling receptors to ion channels and might underlie PTX-insensitive ion channel modulation observed in neurons under physiological and pathological conditions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic Fibers / metabolism*
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Ethylmaleimide / pharmacology
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Protein alpha Subunits*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • GTPase-Activating Proteins
  • Heterotrimeric GTP-Binding Proteins*
  • Ion Channels / metabolism*
  • Male
  • Neurons / metabolism*
  • Neurons / physiology
  • Norepinephrine / pharmacology
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Proteins / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Neurotransmitter / metabolism*
  • Superior Cervical Ganglion / cytology


  • Calcium Channel Blockers
  • Calcium Channels
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Protein alpha Subunits
  • GTPase-Activating Proteins
  • Gnaz protein, rat
  • Ion Channels
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Proteins
  • Receptors, Neurotransmitter
  • GTP-Binding Proteins
  • Heterotrimeric GTP-Binding Proteins
  • Ethylmaleimide
  • Calcium
  • Norepinephrine