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Modulation of intracellular calcium influences capsaicin‐induced currents of TRPV‐1and voltage‐activated channel currents in nociceptive neurones
Author(s) -
Hagenacker Tim,
Büsselberg Dietrich
Publication year - 2007
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1529-8027.2007.00149.x
Subject(s) - trpv , chemistry , biophysics , transient receptor potential channel , calcium , divalent , capsaicin , extracellular , intracellular , voltage dependent calcium channel , calcium in biology , trpv1 , receptor , biochemistry , biology , organic chemistry
Modulation of intracellular calcium ([Ca 2+ ] 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 [Ca 2+ ] i by Ca 2+ entry from the extracellular space, as well as by Ca 2+ release from intracellular stores, the Ca 2+ 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 [ I TRPV‐1 and I Ca(V) ], we performed voltage clamp experiments using Ba 2+ as well as Ca 2+ 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 [ I TRPV‐1 and I Ca(V) ] were measured either when Ca 2+ release from intracellular stores was pharmacologically promoted or prevented. With Ba 2+ as the divalent charge carrier, capsaicin (0.5 μM) 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 Ca 2+ 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 [Ca 2+ ] i by releasing Ca 2+ 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 Ca 2+ release from the stores by dantrolene (5 μM) 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.