G-proteins and G-protein subunits mediating cholinergic inhibition of N-type calcium currents in sympathetic neurons

Eur J Neurosci. 1998 May;10(5):1654-66. doi: 10.1046/j.1460-9568.1998.00170.x.


One postsynaptic action of the transmitter acetylcholine in sympathetic ganglia is to inhibit somatic N-type Ca2+ currents: this reduces Ca2+-activated K+ currents and facilitates high-frequency spiking. Previous experiments on rat superior cervical ganglion neurons have revealed two distinct pathways for this inhibitory action: a rapid, voltage-dependent inhibition through activation of M4 muscarinic acetylcholine receptors (mAChRs), and a slower, voltage-independent inhibition via M1 mAChRs [Hille (1994) Trends in Neurosci., 17, 531-536]. We have analysed the mechanistic basis for this divergence at the level of the individual G-proteins and their alpha and betagamma subunits, using a combination of site-directed antibody injection, plasmid-driven antisense RNA expression, overexpression of selected constitutively active subunits, and antagonism of endogenously liberated betagamma subunits by over-expression of Dy-binding P-adrenergic receptor kinase 1 (PARK1) peptide. The results indicate that: (i) M4 mAChR-induced inhibition is mediated by GoA; (ii) a and Py subunits released from the activated GoA heterotrimer produce separate voltage-insensitive and voltage-sensitive components of inhibition, respectively; and (iii) voltage-insensitive M1 mAChR-induced inhibition is likely to be mediated by the alpha subunit of Gq. Hence, Ca2+ current inhibition results from the concerted, but independent actions of three different G-protein subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / physiology*
  • Cells, Cultured
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / physiology*
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Peptide Fragments / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / physiology*
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / physiology*
  • Virulence Factors, Bordetella / pharmacology


  • Calcium Channels
  • Peptide Fragments
  • Receptors, Muscarinic
  • Virulence Factors, Bordetella
  • GTP-Binding Proteins