Expression and function of a CP339,818-sensitive K+ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia

Luigi Sforna, Maria Cristina D’Adamo, Ilenio Servettini, Luca Guglielmi, Mauro Pessia, Fabio Franciolini, Luigi Catacuzzeno

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K+ current (IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K+ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 µM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation (IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation (IDRKs).

Original languageEnglish
Pages (from-to)2653-2665
Number of pages13
JournalJournal of Neurophysiology
Volume113
Issue number7
DOIs
Publication statusPublished - Apr 1 2015
Externally publishedYes

Keywords

  • Afterhyperpolarization
  • CP339,818
  • Nociceptors
  • Trigeminal ganglion neurons
  • Voltage-gated K currents

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology

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