The receptor-dependent and non-receptor-dependent mechanism of melatonin activated BK channels in middle cerebral artery myocyte / 中国应用生理学杂志

ABSTRACT

OBJECTIVE@#To investigate the mechanisms through which myocyte large-conductance Ca-activated K (BK) 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 BK channel and voltage-gated potassium (K) channel before and after adding melatonin. Currents density of melatonin on BK 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 BK channel were detected before and after the addition of melatonin in the internal-outward mode.@*RESULTS@#① Melatonin markedly increased the whole-cell BK channel current density but not the voltage-gated potassium (K) channel current density. ② Luzindole (1 μmol/L) greatly suppressed melatonin-induced increase of BK channel current density. ③ The Po of BK 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 BK channel, and Tc was reduced much more than To.@*CONCLUSIONS@#Melatonin mediates vasodilation of MCA through the activation of BK channels both melatonin receptor dependent and independent mode.