BACKGROUND: Dexmedetomidine is a highly selective α2-adrenoreceptor agonist with sedative, analgesic and sympatholytic properties. Its cardiac protective effect cannot be ignored, notwithstanding its associated adverse drug reactions. This study aimed to investigate the effects of dexmedetomidine on L-type calcium current (ICa-L) in adult rat ventricular myocytes, and to clarify the electrophysiological mechanism of its effect on cardiomyocytes. METHODS: Single rat ventricular myocytes were obtained by enzymatic dissociation method. Myocytes were perfused with external solutions containing various concentrations of dexmedetomidine at a flow rate of 2-3 ml/min for 5 min. Whole-cell current recordings were performed using the conventional whole-cell patch-clamp technique. Besides, the effects of 1 μM yohimbine, an alpha-2 adrenergic antagonist, were given alone or in combination with 10 ng/ml dexmedetomidine. RESULTS: Dexmedetomidine inhibited the amplitude of ICa-L in a concentration-dependent manner. The current voltage curve was shifted upwards. The steady activated curves were shifted to the right and the V1/2 activation of the ICa-L were increased by dexmedetomidine at the high concentration (10 and 200 ng/ml). Dexmedetomidine did not affect the ICa-L steady-state inactivation curve, but shifted down the recovery curve. Yohimbine did not have influence on ICa-L. However, inhibition of ICa-L by dexmedetomidine at the concentration of 10 ng/ml was partially reversed by yohimbine. CONCLUSIONS: Dexmedetomidine can attenuate ICa-L in adult rat ventricular myocytes, which may contribute to its negative effects on myocardia contractility and cardiac electrophysiology. Its inhibitory effect on ICa-L is partially associated with alpha-2 adrenergic receptors. KEY WORDS: Cardiology; Dexmedetomidine; L-type calcium current; Ventricular myocytes; Whole-cell patch clamp.
BACKGROUND:Dexmedetomidine is a highly selective α2-adrenoreceptor agonist with sedative, analgesic and sympatholytic properties. Its cardiac protective effect cannot be ignored, notwithstanding its associated adverse drug reactions. This study aimed to investigate the effects of dexmedetomidine on L-type calcium current (ICa-L) in adult rat ventricular myocytes, and to clarify the electrophysiological mechanism of its effect on cardiomyocytes. METHODS: Single rat ventricular myocytes were obtained by enzymatic dissociation method. Myocytes were perfused with external solutions containing various concentrations of dexmedetomidine at a flow rate of 2-3 ml/min for 5 min. Whole-cell current recordings were performed using the conventional whole-cell patch-clamp technique. Besides, the effects of 1 μM yohimbine, an alpha-2 adrenergic antagonist, were given alone or in combination with 10 ng/ml dexmedetomidine. RESULTS:Dexmedetomidine inhibited the amplitude of ICa-L in a concentration-dependent manner. The current voltage curve was shifted upwards. The steady activated curves were shifted to the right and the V1/2 activation of the ICa-L were increased by dexmedetomidine at the high concentration (10 and 200 ng/ml). Dexmedetomidine did not affect the ICa-L steady-state inactivation curve, but shifted down the recovery curve. Yohimbine did not have influence on ICa-L. However, inhibition of ICa-L by dexmedetomidine at the concentration of 10 ng/ml was partially reversed by yohimbine. CONCLUSIONS:Dexmedetomidine can attenuate ICa-L in adult rat ventricular myocytes, which may contribute to its negative effects on myocardia contractility and cardiac electrophysiology. Its inhibitory effect on ICa-L is partially associated with alpha-2 adrenergic receptors. KEY WORDS: Cardiology; Dexmedetomidine; L-type calcium current; Ventricular myocytes; Whole-cell patch clamp.
Authors: Gregory B Hammer; David R Drover; Hong Cao; Ethan Jackson; Glyn D Williams; Chandra Ramamoorthy; George F Van Hare; Alisa Niksch; Anne M Dubin Journal: Anesth Analg Date: 2008-01 Impact factor: 5.108
Authors: Constantinos Chrysostomou; Lee Beerman; Dana Shiderly; Donald Berry; Victor O Morell; Ricardo Munoz Journal: Anesth Analg Date: 2008-11 Impact factor: 5.108
Authors: Mei Yuan; Xiao-Wen Meng; Jiao Ma; Hong Liu; Shao-Yong Song; Qing-Cai Chen; Hua-Yue Liu; Juan Zhang; Nan Song; Fu-Hai Ji; Ke Peng Journal: Drug Des Devel Ther Date: 2019-09-02 Impact factor: 4.162
Authors: Christian Ellermann; Jonas Brandt; Julian Wolfes; Kevin Willy; Felix K Wegner; Patrick Leitz; Philipp S Lange; Florian Reinke; Lars Eckardt; Gerrit Frommeyer Journal: Sci Rep Date: 2021-12-14 Impact factor: 4.379