title: Expression and function of a CP339,818-sensitive K⁺ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia.
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).
authors: Dipartimento di Chimica, Biologia e Biotecnologie, Universitá di Perugia, Perugia, Italy; and.
authors: Luigi
authors: L
authors: Sforna
authors: Dipartimento di Medicina Sperimentale, Facoltá di Medicina e Chirurgia, Universitá di Perugia, Perugia, Italy.
authors: Maria Cristina
authors: MC
authors: D'Adamo
authors: Dipartimento di Medicina Sperimentale, Facoltá di Medicina e Chirurgia, Universitá di Perugia, Perugia, Italy.
authors: Ilenio
authors: I
authors: Servettini
authors: Dipartimento di Medicina Sperimentale, Facoltá di Medicina e Chirurgia, Universitá di Perugia, Perugia, Italy.
authors: Luca
authors: L
authors: Guglielmi
authors: Dipartimento di Medicina Sperimentale, Facoltá di Medicina e Chirurgia, Universitá di Perugia, Perugia, Italy.
authors: Mauro
authors: M
authors: Pessia
authors: Dipartimento di Chimica, Biologia e Biotecnologie, Universitá di Perugia, Perugia, Italy; and.
authors: Fabio
authors: F
authors: Franciolini
authors: Dipartimento di Chimica, Biologia e Biotecnologie, Universitá di Perugia, Perugia, Italy; and luigi.catacuzzeno@unipg.it.
authors: Luigi
authors: L
authors: Catacuzzeno
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000502:physiology*; D007097:Imines; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D011804:Quinolines / Q000008:administration & dosage* / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus
chemical_list: D000634:Aminoquinolines; C529069:CP-339,818; D051668:Delayed Rectifier Potassium Channels; D007097:Imines; D011804:Quinolines
keywords: CP339,818; afterhyperpolarization; nociceptors; trigeminal ganglion neurons; voltage-gated K+ currents
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