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CJAP ›› 2018, Vol. 34 ›› Issue (5): 470-475.doi: 10.12047/j.cjap.5675.2018.107

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The receptor-dependent and non-receptor-dependent mechanism of melatonin activated BKCa channels in middle cerebral artery myocyte

CHEN Yu, XU Zhao-xia, ZHANG Hui-rong, WU Ying, SHI Li-jun   

  1. Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China
  • Received:2018-01-09 Revised:2018-09-25 Online:2018-09-28 Published:2019-02-21
  • Supported by:
    国家自然科学基金(31771312,31371201);北京市自然科学基金(5172023)

Abstract: Objective: To investigate the mechanisms through which myocyte large-conductance Ca2+-activated K+ (BKCa) channels mediate the vasodilation effects of melatonin on cerebral arteries (CAs). Methods: Middle cerebral arteries (MCA) were obtained from 8-week-old male Wistar rats after anaesthetized. Middle cerebral arterial smooth muscle cells were enzymatically isolated. Whole cell recording mode of patch clamp technique was used to measure the current density of BKCa channel and voltage-gated potassium (KV) channel before and after adding melatonin. Currents density of melatonin on BKCa channels with melatonin receptor inhibitor 2-phenyl-N-acetyl (luzindole) was recorded using whole cell recording mode and open probability (Po) was recorded using single-channel attached recording mode. The conductance (G) and average open time (To) and off time (Tc) of the BKCa channel were detected before and after the addition of melatonin in the internal-outward mode. Results: ① Melatonin markedly increased the whole-cell BKCa channel current density but not the voltage-gated potassium (KV) channel current density. ② Luzindole (1 μmol/L) greatly suppressed melatonin-induced increase of BKCa channel current density. ③ The Po of BKCa channel was significantly increased by melatonin (100 μmol/L) under cell attached recording mode, which was markedly inhibited by luzindole (1 μmol/L). ④ In inside-outside recording mode, melatonin (1 μmol/L, 100 μmol/L) reduced both To and Tc of BKCa channel, and Tc was reduced much more than To. Conclusion: Melatonin mediates vasodilation of MCA through the activation of BKCa channels via both melatonin receptor dependent and independent mode.

Key words: melatonin, BKCa channel, middle cerebral artery, melatonin receptor, rats

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