ROLE OF A CA2-DEPENDENT SLOW AFTERHYPERPOLARIZATION IN PROSTAGLANDIN E(2)-INDUCED SENSITIZATION OF CULTURED RAT SENSORY NEURONS()

To determine if inhibition of a Ca2+-dependent slow after hyperpolariz ation (AHP(slow)) contributes to prostaglandin E(2) (PGE(2))-induced s ensitization of DRG neurons, we have used patch-clamp electrophysiolog ical techniques on cultured dorsal root ganglion (DRG) neurons from th e adult rat. In support of a role for AHP(slow) in sensitization of DR G neurons, we demonstrate that: (1) AHP(slow) expression is restricted to a subpopulation of putative nociceptors; (2) burst duration is con trolled by AHP(slow) in these neurons; and (3) in some neurons, PGE(2) decreases AHP(slow) and produces a concomitant increase in the number of action potentials generated in response to depolarizing current in jection. However, our results also demonstrate that AHP(slow) modulati on is not sufficient to explain PGE(2)-induced sensitization in the ma jority of DRG neurons because: (1) the size of the population of DRG n eurons expressing AHP(slow) is less than half the size of the populati on of DRG neurons sensitized by PGE(2); (2) PGE(2) 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 AHP(slow) has little effect on threshold; and (3) the sensitizing e ffects of PGE(2) are dissociated from its effects on AHP(slow) in more than half of neurons tested. We conclude that PGE(2)-induced sensitiz ation must involve the modulation of ionic currents in addition to tha t underlying AHP(slow).