Local anaesthetic blockade of neuronal nicotinic ACh receptor-channels in rat parasympathetic ganglion cells

Br J Pharmacol. 1994 Mar;111(3):663-72. doi: 10.1111/j.1476-5381.1994.tb14789.x.


1 The effects of the local anaesthetics QX-222 and procaine on nicotinic acetylcholine (ACh)-evoked currents in cultured parasympathetic cardiac neurones of the rat were investigated by use of the whole-cell, perforated-patch, and outside-out recording configurations of the patch clamp method. 2 QX-222 and procaine, applied to the extracellular surface, reversibly inhibited the peak amplitude of the whole-cell nicotinic ACh-evoked current in a concentration-dependent manner, with half-maximal inhibitory concentrations (IC50) of 28 microM and 2.8 microM, respectively, at -80 mV. In these neurones, the sustained inward current mediated by M1 muscarinic receptor activation was unaltered by QX-222, and neither local anaesthetic affected the adenosine 5'-triphosphate (ATP)-evoked current. 3 QX-222 and procaine block of nicotinic ACh-evoked inward current was voltage-dependent and enhanced by hyperpolarization. An e-fold change in their dissociation equilibrium constants (Kd) resulted from a 62 mV and a 122 mV change in membrane potential, respectively. 4 Both local anaesthetics produce a concentration-dependent increase in the half-time of decay of the nicotinic ACh-evoked inward current. 5 Measurements of unitary currents in outside-out patches showed that QX-222 reversibly increased the mean burst duration and closed time and reduced the mean channel open time and open-state probability of the nicotinic ACh receptor-channel (AChR) in a concentration-dependent manner. 6 The Kd and voltage sensitivity of local anaesthetic block of the nicotinic AChR in rat intracardiac neurones suggests that the pore-forming region of this channel differs from that of the AChR in frog and rat skeletal muscle and from the neuronal alpha 4 beta 2 ACh receptor-channel.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Acetylcholine / physiology
  • Animals
  • Cells, Cultured
  • Ganglia, Parasympathetic / drug effects*
  • Ganglia, Parasympathetic / physiology
  • Ganglia, Parasympathetic / ultrastructure*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Ion Channels / drug effects*
  • Ion Channels / physiology*
  • Kinetics
  • Lidocaine / analogs & derivatives*
  • Lidocaine / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / drug effects*
  • Neurons / physiology
  • Neurons / ultrastructure*
  • Nicotinic Antagonists*
  • Procaine / pharmacology*
  • Rats
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology
  • Receptors, Nicotinic / physiology*


  • Ion Channels
  • Nicotinic Antagonists
  • Receptors, Muscarinic
  • Receptors, Nicotinic
  • QX-222
  • Procaine
  • Lidocaine
  • Acetylcholine