Effectiveness in block by dexmedetomidine of hyperpolarization-activated cation current, independent of its agonistic effect on α2-adrenergic receptors

Te Ling Lu, Te Jung Lu, Sheng Nan Wu

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)

摘要

Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors, has been tailored for sedation without risk of respiratory depression. Our hypothesis is that DEX produces any direct perturbations on ionic currents (e.g., hyperpolarization-activated cation current, Ih). In this study, addition of DEX to pituitary GH3 cells caused a time-and concentration-dependent reduction in the amplitude of Ih with an IC50 value of 1.21 µM and a KD value of 1.97 µM. A hyperpolarizing shift in the activation curve of Ih by 10 mV was observed in the presence of DEX. The voltage-dependent hysteresis of Ih elicited by long-lasting triangular ramp pulse was also dose-dependently reduced during its presence. In continued presence of DEX (1 µM), further addition of OXAL (10 µM) or replacement with high K+ could reverse DEX-mediated inhibition of Ih, while subsequent addition of yohimbine (10 µM) did not attenuate the inhibitory effect on Ih amplitude. The addition of 3 µM DEX mildly suppressed the amplitude of erg-mediated K+ current. Under current-clamp potential recordings, the exposure to DEX could diminish the firing frequency of spontaneous action potentials. In pheochromocytoma PC12 cells, DEX was effective at suppressing Ih together with a slowing in activation time course of the current. Taken together, findings from this study strongly suggest that during cell exposure to DEX used at clinically relevant concentrations, the DEX-mediated block of Ih appears to be direct and would particularly be one of the ionic mechanisms underlying reduced membrane excitability in the in vivo endocrine or neuroendocrine cells.

原文English
文章編號9110
頁(從 - 到)1-18
頁數18
期刊International journal of molecular sciences
21
發行號23
DOIs
出版狀態Published - 2020 十二月 1

All Science Journal Classification (ASJC) codes

  • 催化
  • 分子生物學
  • 光譜
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學
  • 無機化學

指紋

深入研究「Effectiveness in block by dexmedetomidine of hyperpolarization-activated cation current, independent of its agonistic effect on α<sub>2</sub>-adrenergic receptors」主題。共同形成了獨特的指紋。

引用此