期刊
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
卷 12, 期 4, 页码 277-284出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1529-8027.2007.00149.x
关键词
capsaicin; intracellular calcium; nociception; TRPV-1; voltage-activated calcium channel currents
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 [ITRPV-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 mu M capsaicin, and the currents through TRPV-1 and VACC [ITRPV-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 mu M) 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 ITRPV-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 ITRPV-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 mu M) resulted in less pronounced effects [24.5 +/- 8.8%, relative to peak I-Ca(V)] for ITRPV-1, and a reduction to 35.4 +/- 3% of baseline for I-Ca(V) after capsaicin application.
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