Prostaglandin E2 inhibits the potassium current in sensory neurons from hyperalgesic Kv1.1 knockout mice

X. Jiang, Y. H. Zhang, J. D. Clark, B. L. Tempel, Grant Nicol

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Prostaglandin E2 (PGE2) 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 PGE2 can alter the sensitivity of Kcna1-null mice to noxious stimulation and examine the capability of PGE2 to inhibit the potassium current in these knockout mice. Behavioral assays were used to assess the effect of PGE2 on either thermal hyperalgesia or mechanical sensitivities. In addition, the whole-cell patch-clamp technique was used to study the effects of PGE2 on the total potassium current recorded from isolated mouse sensory neurons. Even with a reduced threshold to thermal stimulation, PGE2 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. PGE2 suppressed the total potassium current in both groups of mice by 40-50% without altering the voltage dependence of activation. In addition, PGE2 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 PGE2 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.

Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalNeuroscience
Volume119
Issue number1
DOIs
StatePublished - Jun 18 2003

Fingerprint

Sensory Receptor Cells
Dinoprostone
Knockout Mice
Potassium
Hot Temperature
Delayed Rectifier Potassium Channels
Neurons
Nociceptors
Pain Perception
Potassium Channels
Hyperalgesia
Patch-Clamp Techniques
Pain

Keywords

  • Capsaicin
  • Potassium channel
  • Sensitization
  • Thermal and mechanical stimulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Prostaglandin E2 inhibits the potassium current in sensory neurons from hyperalgesic Kv1.1 knockout mice. / Jiang, X.; Zhang, Y. H.; Clark, J. D.; Tempel, B. L.; Nicol, Grant.

In: Neuroscience, Vol. 119, No. 1, 18.06.2003, p. 65-72.

Research output: Contribution to journalArticle

Jiang, X. ; Zhang, Y. H. ; Clark, J. D. ; Tempel, B. L. ; Nicol, Grant. / Prostaglandin E2 inhibits the potassium current in sensory neurons from hyperalgesic Kv1.1 knockout mice. In: Neuroscience. 2003 ; Vol. 119, No. 1. pp. 65-72.
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