Vasoactive intestinal polypeptide modulation of nicotinic ACh receptor channels in rat intracardiac neurones

J Physiol. 1996 Jun 1;493 ( Pt 2)(Pt 2):503-15. doi: 10.1113/jphysiol.1996.sp021399.


1. The effects of vasoactive intestinal polypeptide (VIP) on isolated parasympathetic neurones of rat intracardiac ganglia were examined under voltage clamp using dialysed and perforated patch whole-cell and excised outside-out membrane patch recording configurations. 2. VIP reversibly potentiated nicotinic ACh-evoked whole-cell currents, with half-maximal potentiation (EC50) obtained with 260 pM VIP. However, VIP had no effect on muscarinic ACh-evoked currents, ATP-evoked currents, or depolarization-activated ionic currents in these neurones. 3. VIP-induced potentiation of nicotinic ACh-evoked whole-cell currents was observed following cell dialysis, and was inhibited reversibly by bath application of the VIP receptor-binding inhibitor L-8-K (5 microM) or the neuronal nicotinic receptor antagonist mecamylamine (3 microM). 4. The signal transduction pathway mediating VIP-induced potentiation of nicotinic ACh-evoked currents involves a guanine nucleotide-binding protein (G-protein) but not cyclic AMP. Intracellular application of 100 microM GDP-beta-S, or pre-incubation of neurones with pertussis toxin, inhibited VIP-induced potentiation of ACh-evoked whole-cell currents. 5. In outside-out membrane patches, co-application of ACh (4 microM) and VIP (4 nM) decreased the duration of closings between bursts and clusters of bursts of ACh single-channel activity relative to control (4 microM, ACh alone). VIP, however, did not alter single ACh receptor channel current amplitude, duration of closings and openings within a burst, or mean burst duration. 6. VIP-induced modification of nicotinic ACh receptor channel kinetics results in an increase in the open-channel probability which is sufficient to account for the VIP-mediated potentiation of nicotinic ACh-evoked whole-cell currents. 7. The potentiation of nicotinic ACh-evoked currents by VIP is likely to account for the altered neuronal activity observed in the mammalian intracardiac ganglia in vivo and consequent changes in heart rate and cardiac contractility.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Electrophysiology
  • GTP-Binding Proteins / metabolism
  • Heart / innervation*
  • In Vitro Techniques
  • Ion Channels / metabolism
  • Ion Channels / physiology*
  • Kinetics
  • Membrane Potentials / drug effects
  • Myocardium / cytology
  • Myocardium / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nicotinic Agonists / pharmacology*
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / metabolism
  • Patch-Clamp Techniques
  • Pertussis Toxin
  • Rats
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism*
  • Signal Transduction / drug effects
  • Vasoactive Intestinal Peptide / pharmacology*
  • Virulence Factors, Bordetella / pharmacology


  • Ion Channels
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Virulence Factors, Bordetella
  • Vasoactive Intestinal Peptide
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Acetylcholine