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  • Title: Modulation of intracellular calcium influences capsaicin-induced currents of TRPV-1 and voltage-activated channel currents in nociceptive neurones.
    Author: Hagenacker T, Büsselberg D.
    Journal: J Peripher Nerv Syst; 2007 Dec; 12(4):277-84. PubMed ID: 18042138.
    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 [Ca2+](i) and the activation of TRPV-1 receptor and VACC currents [I(TRPV-1) and I(Ca(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 microM capsaicin, and the currents through TRPV-1 and VACC [I(TRPV-1) and I(Ca(V))] were measured either when Ca2+ release from intracellular stores was pharmacologically promoted or prevented. With Ba2+ as the divalent charge carrier, capsaicin (0.5 microM) reduced I(Ca(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 I(Ca(V))]. These currents were significantly different when Ca2+ was used as charge carrier: the I(Ca(V)) reductions were decreased to 17.8 +/- 5.9% of baseline, while the I(TRPV-1) was as high as 57.1 +/- 9.1% of I(Ca(V)). Increases of [Ca2+](i) by releasing Ca2+ from intracellular stores (using caffeine, 10 mM) before the application of capsaicin increased the I(TRPV-1) (14.1 +/- 7%), while the I(Ca(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 microM) resulted in less pronounced effects [24.5 +/- 8.8%, relative to peak I(Ca(V))] for I(TRPV-1), and a reduction to 35.4 +/- 3% of baseline for I(Ca(V)) after capsaicin application.
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