PROSTAGLANDINS SUPPRESS AN OUTWARD POTASSIUM CURRENT IN EMBRYONIC RATSENSORY NEURONS

The cellular mechanisms giving rise to the enhanced excitability induc ed by prostaglandin E(2) (PGE(2)) and carba prostacyclin (CPGI(2)) in embryonic rat sensory neurons were investigated using the whole cell p atch-clamp recording technique. Exposing sensory neurons to 1 mu M PGE (2) produced a twofold increase in the number of action potentials eli cited by a ramp of depolarizing current, but this eicosanoid had no ef fect on the resting membrane potential or the amplitude of the slow af terhyperpolarization. Characterization of the outward potassium curren ts in the embryonic sensory neurons indicated that the composition of the total current was variable among these neurons. A steady-state ina ctivation protocol was used to determine the extent of residual nonina ctivating current. A conditioning prepulse to +20 mV demonstrated that some of these neurons exhibited only a sustained potassium current wi th little steady-state inactivation whereas others exhibited some comb ination of a sustained as well as a rapidly inactivating I-A-type curr ent. Treatment with 1 mu M PGE(2) or 1 mu M CPGI(2), but not 1 mu M pr ostaglandin F-2 alpha (PGF(2 alpha)) produced a time-dependent suppres sion of the total potassium current. After a 20-min exposure, PGE(2) a nd CPGI(2) inhibited the maximal current obtained at +60 mV by 48 and 40%, respectively. The prostaglandin-induced suppression of the potass ium current was not associated with a shift in the voltage dependence for activation. Subtraction of the currents remaining after PGE(2) or CPGI(2) treatment from their respective control recordings revealed th at the prostaglandin-sensitive current had characteristics that were c onsistent with a sustained-type of potassium current. This idea is sup ported by the following observation. The steady-state inactivation pro tocol revealed that for prepulse voltages activating both rapidly inac tivating and sustained currents, the relaxation of the current was acc elerated after treatment with PGE(2) or CPGI(2) suggesting the removal of a slower component. This effect was not observed in neurons exhibi ting only the sustained type current. These results suggest that pro-i nflammatory prostaglandins enhance the excitability of rat sensory neu rons, in part, through the suppression of an outward potassium current that may modulate the firing threshold for generation of the action p otential.