PROSTAGLANDINS SUPPRESS AN OUTWARD POTASSIUM CURRENT IN EMBRYONIC RAT
Nicol, G.D., M.R. Vasko, and A.R. Evans.
Department of Pharmacology & Toxicology and Department of Anesthesia
635 Barnhill Drive, School of Medicine, Indiana University, Indianapolis, IN
APStracts 3:0210N, 1996.
The cellular mechanisms giving rise to the enhanced excitability induced by
prostaglandin E 2 (PGE 2 ) and carba prostacyclin (CPGI 2 ) in embryonic rat
sensory neurons were investigated using the whole-cell patch-clamp recording
technique. Exposing sensory neurons to 1 [mu]M PGE 2 produced a two-fold
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 non-
inactivating 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 [mu]M PGE 2 or 1 [mu]M CPGI 2 , but not 1 [mu]M prostaglandin F 2[alpha]
(PGF 2[alpha] ) produced a time-dependent suppression of the total potassium
current. After a 20 min exposure, PGE 2 and CPGI 2 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 PGE 2 or CPGI 2 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 PGE 2 or CPGI 2 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 AP.
Received 2 July 1996; accepted in final form 13 September 1996.
APS Manuscript Number J516-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996