Modulation of intracellular calcium influences capsaicin-induced currents of TRPV-1and voltage-activated channel currents in nociceptive neurones

Tim Hagenacker, Dietrich Büsselberg

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Modulation of intracellular calcium ([Ca2+]i) has a major impact on processing of nociceptive signals. While activation of the transient receptor potential vanilloid-1 (TRPV-1) receptor/channel complex increases [Ca2+]i by Ca2+ entry from the extracellular space, as well as by Ca2+ release from intracellular stores, the Ca2+ entry through voltage-activated calcium channels (VACCs) is modulated simultaneously. To clarify the relations between [Ca 2+]i and the activation of TRPV-1 receptor and VACC currents [ITRPV-1 and ICa(V)], we performed voltage clamp experiments using Ba2+ as well as Ca2+ as a charge carrier. The TRPV-1 receptor was activated by the application of 0.5 μM capsaicin, and the currents through TRPV-1 and VACC [ITRPV-1 and ICa(V)] were measured either when Ca2+ release from intracellular stores was pharmacologically promoted or prevented. With Ba 2+ as the divalent charge carrier, capsaicin (0.5 μM) reduced ICa(V) (elicited by a depolarization to 0 mV) to 52.7 ± 4.5% of baseline, and the elicited current through the TRPV-1 receptor/channel complex was 6.6 ± 0.9% [relative to peak ICa(V)]. These currents were significantly different when Ca2+ was used as charge carrier: the ICa(V) reductions were decreased to 17.8 ± 5.9% of baseline, while the ITRPV-1 was as high as 57.1 ± 9.1% of ICa(V). Increases of [Ca2+]i by releasing Ca2+ from intracellular stores (using caffeine, 10 mM) before the application of capsaicin increased the ITRPV-1 (14.1 ± 7%), while the ICa(V) was decreased to 51.6 ± 4.9% compared with control. A preexperimental partial reduction of the Ca2+ release from the stores by dantrolene (5 μM) resulted in less pronounced effects [24.5 ± 8.8%, relative to peak ICa(V)] for ITRPV-1, and a reduction to 35.4 ± 3% of baseline for ICa(V) after capsaicin application.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalJournal of the Peripheral Nervous System
Volume12
Issue number4
DOIs
Publication statusPublished - 1 Dec 2007

    Fingerprint

Keywords

  • Capsaicin
  • Intracellular calcium
  • Nociception
  • TRPV-1
  • Voltage-activated calcium channel currents

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this