PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade

J Physiol. 1996 Sep 1;495 ( Pt 2)(Pt 2):429-40. doi: 10.1113/jphysiol.1996.sp021604.


1. In current-clamp recordings, 1 microM prostaglandin E2 (PGE2) increased the excitability of neonatal rat dorsal root ganglion neurones. The current threshold for firing was reduced, and the response to a constant suprathreshold stimulation was modified such that a single evoked action potential was converted to a train of action potentials. The excitatory action of PGE2 was still apparent when action potentials were evoked in the presence of 500 nM tetrodotoxin. 2. In voltage-clamp experiments 1 microM PGE2 frequently increased the magnitude of the peak currents recorded, and caused a hyperpolarizing shift (of approximately 6 mV) in the activation curve for the tetrodotoxin-resistant sodium current (TTX-R INa). In some cells, the hyperpolarizing shift in the activation curve was accompanied by a decrease in peak conductance. PGE2 also caused a hyperpolarizing shift in the steady-state inactivation curve for the sodium current. 3. Extracellular application of the cAMP analogue dibutyryl cAMP (dbcAMP) at a concentration of 1 mM produced effects on both the current-voltage relationship and the steady-state inactivation curve for the TTX-R INa which were indistinguishable from those observed with PGE2. Prior exposure of the neurones to dbcAMP occluded the effect of a subsequent treatment with PGE2. 4. Forskolin (10 microM), a direct activator of adenylate cyclase, mimicked the effects of PGE2 and dbcAMP on TTX-R INa. The inactive congener of forskolin, 1, 9-dideoxyforskolin (10 microM), reduced the amplitude of TTX-R INa, but did not evoke a hyperpolarizing shift in the activation curve. 5. Intracellular perfusion of the neurones with an inhibitor of protein kinase A inhibited the effect of PGE2 on TTX-R INa. 6. PGE2 also reduced the amplitude of voltage-gated potassium currents (IK), which will contribute to the excitatory action. The mechanisms underlying the changes in IK have yet to be elucidated. 7. We propose that the PGE2-mediated increase in excitability in sensory neurones may be due, at least in part, to the cAMP-protein kinase A-dependent modulation of the tetrodotoxin-resistant sodium channel.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Animals, Newborn / physiology*
  • Bucladesine / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dinoprostone / physiology*
  • Electrophysiology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / enzymology
  • Ganglia, Spinal / metabolism*
  • In Vitro Techniques
  • Membrane Potentials / physiology
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism*
  • Tetrodotoxin / pharmacology*


  • Sodium Channels
  • Colforsin
  • Tetrodotoxin
  • Bucladesine
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Dinoprostone