Role of a Ca(2+)-dependent slow afterhyperpolarization in prostaglandin E2-induced sensitization of cultured rat sensory neurons.
To determine if inhibition of a Ca(2+)-dependent slow afterhyperpolarization (AHPslow) contributes to prostaglandin E2 (PGE2)-induced sensitization of DRG neurons, we have used patch-clamp electrophysiological techniques on cultured dorsal root ganglion (DRG) neurons from the adult rat. In support of a role for AHPslow in sensitization of DRG neurons, we demonstrate that: (1) AHPslow expression is restricted to a subpopulation of putative nociceptors; (2) burst duration is controlled by AHPslow in these neurons; and (3) in some neurons, PGE2 decreases AHPslow and produces a concomitant increase in the number of action potentials generated in response to depolarizing current injection. However, our results also demonstrate that AHPslow modulation is not sufficient to explain PGE2-induced sensitization in the majority of DRG neurons because: (1) the size of the population of DRG neurons expressing AHPslow is less than half the size of the population of DRG neurons sensitized by PGE2; (2) PGE2 produces a decrease in action potential threshold as well as an increase in the number of action potentials in response to current injection, while inhibition of AHPslow has little effect on threshold; and (3) the sensitizing effects of PGE2 are dissociated from its effects on AHPslow in more than half of neurons tested. We conclude that PGE2-induced sensitization must involve the modulation of ionic currents in addition to that underlying AHPslow.
Gold
M S
MS
Neuroscience Program, University of California, Los Angeles 90024, USA.
Shuster
M J
MJ
Levine
J D
JD
D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013997:Time Factors
D015232:Dinoprostone; D011188:Potassium; D002118:Calcium