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L-type calcium channel gating is modulated by bradykinin with a PKC-dependent mechanism in NG108-15 cells

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Abstract

Bradykinin (BK) excites dorsal root ganglion cells, leading to the sensation of pain. The actions of BK are thought to be mediated by heterotrimeric G protein-regulated pathways. Indeed there is strong evidence that in different cell types BK is involved in phosphoinositide breakdown following activation of Gq/11. In the present study we show that the Ca2+ current flowing through L-type voltage-gated Ca2+ channels in NG108-15 cells (differentiated in vitro to acquire a neuronal phenotype), measured using the whole-cell patch clamp configuration, is reversibly inhibited by BK in a voltage-independent fashion, suggesting a cascade process where a second messenger system is involved. This inhibitory action of BK is mimicked by the application of 1,2-oleoyl-acetyl glycerol (OAG), an analog of diacylglycerol that activates PKC. Interestingly, OAG occluded the effects of BK and both effects were blocked by selective PKC inhibitors. The down modulation of single L-type Ca2+ channels by BK and OAG was also investigated in cell-attached patches. Our results indicate that the inhibitory action of BK involves activation of PKC and mainly shows up in a significant reduction of the probability of channel opening, caused by an increase and clustering of null sweeps in response to BK.

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Acknowledgements

This work was supported by grants from Miur (FIRB 2001 and PRIN 2002) and INFM to M.T.

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  1. Dipartimento di Scienze Fisiologiche e Farmacologiche Cellulari e Molecolari and INFM, Universita’ di Pavia, Via Forlanini 6, 27100, Pavia, Italy

    Mauro Toselli & Vanni Taglietti

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  1. Mauro Toselli
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  2. Vanni Taglietti
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Correspondence to Mauro Toselli.

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Toselli, M., Taglietti, V. L-type calcium channel gating is modulated by bradykinin with a PKC-dependent mechanism in NG108-15 cells. Eur Biophys J 34, 217–229 (2005). https://doi.org/10.1007/s00249-004-0444-x

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