Prostaglandin E2 inhibits the potassium current in sensory neurons from hyperalgesic Kv1.1 knockout mice.
Prostaglandin E(2) (PGE(2)) enhances the sensitivity of sensory neurons to various forms of noxious stimulation. This occurs, in part, by the suppression of a delayed rectifier-like potassium current in these neurons. However, the molecular identity of this current remains unclear. Recent studies demonstrated that a mutant mouse lacking a delayed rectifier potassium channel gene, Kv1.1, displayed lowered thresholds to thermal stimulation in behavioral assays of pain perception, i.e. the Kcna1-null mice were hyperalgesic. Here we examined whether PGE(2) can alter the sensitivity of Kcna1-null mice to noxious stimulation and examine the capability of PGE(2) to inhibit the potassium current in these knockout mice. Behavioral assays were used to assess the effect of PGE(2) on either thermal hyperalgesia or mechanical sensitivities. In addition, the whole-cell patch-clamp technique was used to study the effects of PGE(2) on the total potassium current recorded from isolated mouse sensory neurons. Even with a reduced threshold to thermal stimulation, PGE(2) could still sensitize the response of Kcna1-null mice to thermal and mechanical stimulation by amounts that were similar to that in wild type mice. The activation properties of the potassium current were similar for both the wild type and the Kcna1-null mice, whereas the inactivation properties were different in cells exhibiting large amounts of steady-state inactivation (>50%) measured at +20 mV. PGE(2) suppressed the total potassium current in both groups of mice by 40-50% without altering the voltage dependence of activation. In addition, PGE(2) produced similar amounts of suppression in both groups of mice when currents were examined with the steady-state inactivation protocol. Based on these results, it is unlikely that Kv1.1 is the molecular identity of the potassium channel(s) modulated by PGE(2) to sensitize nociceptive sensory neurons. Also, the enhanced thermal sensitivity as observed in the Kcna1-null mice might be due to more central neurons of the pain sensing pathway.
Jiang
X
X
Department of Pharmacology and Toxicology, 635 Barnhill Drive, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zhang
Y H
YH
Clark
J D
JD
Tempel
B L
BL
Nicol
G D
GD
D000818:Animals; D001522:Behavior, Animal; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004553:Electric Conductivity; D022062:Electrophysiologic Techniques, Cardiac; D005838:Genotype; D006930:Hyperalgesia; D051662:Kv1.1 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout / Q000235:genetics / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D010812:Physical Stimulation; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011930:Reaction Time; D012684:Sensory Thresholds / Q000187:drug effects; D013997:Time Factors
C496947:Kcna1 protein, mouse; D010120:Oxytocics; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D015232:Dinoprostone