Prostaglandins Suppress an Outward Potassium Current in Embryonic Rat Sensory Neurons

G. D. Nicol, M. R. Vasko, A. R. Evans
1997 Journal of Neurophysiology  
The cellular mechasensitizing action of prostaglandins results from a direct acnisms giving rise to the enhanced excitability induced by prostation on the neuron because pretreatment with prostaglandin glandin E 2 (PGE 2 ) and carba prostacyclin (CPGI 2 ) in embryonic E 2 (PGE 2 ) increased the rate of action potential firing inrat sensory neurons were investigated using the whole cell patchduced by elevated potassium (Baccaglini and Hogan 1983) clamp recording technique. Exposing sensory
more » ... s to 1 mM or by the focal application of bradykinin (Nicol and Cui PGE 2 produced a twofold increase in the number of action poten-1994) in isolated sensory neurons grown in culture. In additials elicited by a ramp of depolarizing current, but this eicosanoid tion, exposure of these isolated sensory neurons grown in had no effect on the resting membrane potential or the amplitude of the slow afterhyperpolarization. Characterization of the outward culture to the pro-inflammatory prostaglandins, PGE 2 or potassium currents in the embryonic sensory neurons indicated that carba prostacyclin, produced a nearly twofold increase in the the composition of the total current was variable among these bradykinin-or capsaicin-evoked release of the neuroactive neurons. A steady-state inactivation protocol was used to determine peptides, substance P and calcitonin gene-related peptide the extent of residual noninactivating current. A conditioning pre- (Hingtgen and Vasko 1994; . Although pulse to /20 mV demonstrated that some of these neurons exhibthe cellular mechanisms generating the prostaglandin-inited only a sustained potassium current with little steady-state inacduced sensitization are unknown, the above results demontivation whereas others exhibited some combination of a sustained strate that treatment with prostaglandins leads to an increase as well as a rapidly inactivating I A -type current. Treatment with 1 mM PGE 2 or 1 mM CPGI 2 , but not 1 mM prostaglandin F 2a (PGF 2a ) in membrane excitability and an increase in the release of produced a time-dependent suppression of the total potassium curneuropeptides from sensory neurons. rent. After a 20-min exposure, PGE 2 and CPGI 2 inhibited the maxi-In Aplysia sensory neurons, a similar form of sensitization mal current obtained at /60 mV by 48 and 40%, respectively. The has been observed (Byrne and Kandel 1996; Byrne et al. prostaglandin-induced suppression of the potassium current was 1993; Kandel and Schwartz 1982) in that exposure to serotonot associated with a shift in the voltage dependence for activation. nin produced an increase in the number of action potentials Subtraction of the currents remaining after PGE 2 or CPGI 2 treatelicited by a depolarizing current (Baxter and Byrne 1990; ment from their respective control recordings revealed that the Critz et al. 1991; Goldsmith and Abrams 1992; Klein et al. prostaglandin-sensitive current had characteristics that were consis-1986; Walters et al. 1983) . Treatment with serotonin also tent with a sustained-type of potassium current. This idea is supported by the following observation. The steady-state inactivation enhanced the release of neurotransmitter from the sensory protocol revealed that for prepulse voltages activating both rapidly neuron (Castellucci and Kandel 1976; Hochner et al. 1986 ; inactivating and sustained currents, the relaxation of the current Klein and Kandel 1980; . This serotoninwas accelerated after treatment with PGE 2 or CPGI 2 suggesting induced sensitization arises, in part, through the inhibition the removal of a slower component. This effect was not observed of multiple potassium currents (see Baxter and Byrne 1989; in neurons exhibiting only the sustained type current. These results Goldsmith and Abrams 1992; Hochner and Kandel 1992; suggest that pro-inflammatory prostaglandins enhance the excit- Klein and Kandel 1980; Siegelbaum et al. 1982) . ability of rat sensory neurons, in part, through the suppression of Although it is well established that modulation of potasan outward potassium current that may modulate the firing threshold for generation of the action potential.
doi:10.1152/jn.1997.77.1.167 pmid:9120557 fatcat:icydnwy4qzd2tbu7jg7bylgsli