The Journal of Neurophysiology Vol. 77 No. 1 January 1997, pp. 167-176
Copyright ©1997 The American Physiological Society

Prostaglandins Suppress an Outward Potassium Current in Embryonic Rat Sensory Neurons

G. D. Nicol¹, M. R. Vasko^{1, 2}, and A. R. Evans¹

¹ Department of Pharmacology and Toxicology and ² Department of Anesthesia, School of Medicine, Indiana University, Indianapolis, Indiana 46202-5120

Nicol, G. D., M. R. Vasko, and A. R. Evans. Prostaglandins suppress an outward potassium current in embryonic rat sensory neurons. J. Neurophysiol. 77: 167-176, 1997. The cellular mechanisms giving rise to the enhanced excitability induced by prostaglandin E₂ (PGE₂) and carba prostacyclin (CPGI₂) in embryonic rat sensory neurons were investigated using the whole cell patch-clamp recording technique. Exposing sensory neurons to 1 µM PGE₂ produced a twofold increase in the number of action potentials elicited by a ramp of depolarizing current, but this eicosanoid had no effect on the resting membrane potential or the amplitude of the slow afterhyperpolarization. Characterization of the outward potassium currents in the embryonic sensory neurons indicated that the composition of the total current was variable among these neurons. A steady-state inactivation protocol was used to determine the extent of residual noninactivating current. A conditioning prepulse to +20 mV demonstrated that some of these neurons exhibited only a sustained potassium current with little steady-state inactivation whereas others exhibited some combination of a sustained as well as a rapidly inactivating I_A-type current. Treatment with 1 µM PGE₂ or 1 µM CPGI₂, but not 1 µM prostaglandin F₂ (PGF₂) produced a time-dependent suppression of the total potassium current. After a 20-min exposure, PGE₂ and CPGI₂ inhibited the maximal current obtained at +60 mV by 48 and 40%, respectively. The prostaglandin-induced suppression of the potassium current was not associated with a shift in the voltage dependence for activation. Subtraction of the currents remaining after PGE₂ or CPGI₂ treatment from their respective control recordings revealed that the prostaglandin-sensitive current had characteristics that were consistent with a sustained-type of potassium current. This idea is supported by the following observation. The steady-state inactivation protocol revealed that for prepulse voltages activating both rapidly inactivating and sustained currents, the relaxation of the current was accelerated after treatment with PGE₂ or CPGI₂ suggesting the removal of a slower component. This effect was not observed in neurons exhibiting only the sustained type current. These results suggest that pro-inflammatory prostaglandins enhance the excitability of rat sensory neurons, in part, through the suppression of an outward potassium current that may modulate the firing threshold for generation of the action potential.

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