کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2533595 | 1559058 | 2010 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Bradykinin-induced depolarisation and Ca2+ influx through voltage-gated Ca2+ channels in rat submucosal neurons Bradykinin-induced depolarisation and Ca2+ influx through voltage-gated Ca2+ channels in rat submucosal neurons](/preview/png/2533595.png)
The aim of the present study was the investigation of the mechanism, by which bradykinin B2 receptor stimulation evokes an increase of the cytosolic Ca2+ concentration in rat submucosal plexus. In ganglionic cells within the intact submucosal plexus, the Ca2+-response evoked by bradykinin was suppressed by Ni2+, suggesting that Ca2+ enters the cell through voltage-gated Ca2+ channels (Cav channels). Inhibition of Cav channel subtypes P, T and R with ω-agatoxin IVA, flunarizine, and SNX-482 did not affect the response to bradykinin. In contrast, verapamil, ω-conotoxin GVIA, and ω-conotoxin MVIIC attenuated the actions of bradykinin, indicating the involvement of the L-, N- and Q-subtypes of Cav channels. The combination of these three blockers had a strong inhibitory action on the bradykinin response. In order to study the mechanism of activation of Cav channels by bradykinin, isolated submucosal neurons in culture were used. Immunocytochemical stainings revealed that these neurons expressed the bradykinin B2 receptor, while the B1 receptor was absent. Isolated submucosal glial cells did not express the bradykinin B2 receptor. Whole-cell patch-clamp measurements of submucosal neurons showed that bradykinin induced a depolarisation of the membrane in average of 14 mV. The ionic mechanism underlying the depolarisation was identified with current measurements at two different membrane potentials (− 81 and 0 mV). The current associated to Na+ influx was not changed by bradykinin, whereas the current representing K+ outflux was reduced by 26%. The present results suggest that at submucosal neurons from the rat colon bradykinin induces a depolarisation by decreasing the K+ conductance, followed by activation of the Cav channels, which mediates the increase of the cytosolic Ca2+ concentration.
Journal: European Journal of Pharmacology - Volume 635, Issues 1–3, 10 June 2010, Pages 87–95