Academic Journal
4-Aminopyridine:a pan voltage-gated potassium channel inhibitor that enhances K v 7.4 currents and inhibits noradrenaline-mediated contraction of rat mesenteric small arteries
| العنوان: | 4-Aminopyridine:a pan voltage-gated potassium channel inhibitor that enhances K v 7.4 currents and inhibits noradrenaline-mediated contraction of rat mesenteric small arteries |
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| المؤلفون: | Khammy, Makhala M., Kim, Sukhan, Bentzen, Bo H., Lee, Soojung, Choi, Inyeong, Aalkjær, Christian, Jepps, Thomas A. |
| المصدر: | Khammy , M M , Kim , S , Bentzen , B H , Lee , S , Choi , I , Aalkjær , C & Jepps , T A 2018 , ' 4-Aminopyridine : a pan voltage-gated potassium channel inhibitor that enhances K v 7.4 currents and inhibits noradrenaline-mediated contraction of rat mesenteric small arteries ' , British Journal of Pharmacology , vol. 175 , no. 3 , pp. 501-516 . https://doi.org/10.1111/bph.14097 |
| سنة النشر: | 2018 |
| المجموعة: | Aarhus University: Research |
| الوصف: | Background and Purpose: K v 7.4 and K v 7.5 channels are regulators of vascular tone. 4-Aminopyridine (4-AP) is considered a broad inhibitor of voltage-gated potassium (K V ) channels, with little inhibitory effect on K v 7 family members at mmol concentrations. However, the effect of 4-AP on K v 7 channels has not been systematically studied. The aim of this study was to investigate the pharmacological activity of 4-AP on K v 7.4 and K v 7.5 channels and characterize the effect of 4-AP on rat resistance arteries. Experimental Approach: Voltage clamp experiments were performed on Xenopus laevis oocytes injected with cRNA encoding KCNQ4 or KCNQ5, HEK cells expressing K v 7.4 channels and on rat, freshly isolated mesenteric artery smooth muscle cells. The effect of 4-AP on tension, membrane potential, intracellular calcium and pH was assessed in rat mesenteric artery segments. Key Results: 4-AP increased the K v 7.4-mediated current in oocytes and HEK cells but did not affect K v 7.5 current. 4-AP also enhanced native mesenteric artery myocyte K + current at sub-mmol concentrations. When applied to NA-preconstricted mesenteric artery segments, 4-AP hyperpolarized the membrane, decreased [Ca 2+ ] i and caused concentration-dependent relaxations that were independent of 4-AP-mediated changes in intracellular pH. Application of the K v 7 channel blocker XE991 and BK Ca channel blocker iberiotoxin attenuated 4-AP-mediated relaxation. 4-AP also inhibited the NA-mediated signal transduction to elicit a relaxation. Conclusions and Implications: These data show that 4-AP is able to relax NA-preconstricted rat mesenteric arteries by enhancing the activity of K v 7.4 and BK Ca channels and attenuating NA-mediated signalling. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/bph.14097 |
| الاتاحة: | https://pure.au.dk/portal/da/publications/4aminopyridine(d8f791a9-4b23-4f78-8637-2c237de38f43).html https://doi.org/10.1111/bph.14097 http://www.scopus.com/inward/record.url?scp=85040741037&partnerID=8YFLogxK https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773965/pdf/BPH-175-501.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7BDD8283 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/bph.14097 |
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