Dexmedetomidine Exerts a Negative Chronotropic Action on Sinoatrial Node Cells Through the Activation of Imidazoline Receptors. Issue 6 (December 2021)

• Record Type: Journal Article
• Authors: Ishihara, Mariko; Kojima, Akiko; Ding, Wei-Guang; Kitagawa, Hirotoshi; Matsuura, Hiroshi
• Is Part Of: Journal of cardiovascular pharmacology. Volume 78:Issue 6(2021)
• Publication Date: 2021-12
• Subjects: dexmedetomidine -- α2-adrenoceptor -- imidazoline receptor -- sinoatrial node cells -- hyperpolarization-activated cation current -- automaticity; Cardiovascular Diseases -- drug therapy -- Periodicals; Cardiovascular System -- drug effects -- Periodicals; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular agents; Cardiovascular pharmacology; Periodicals; 615.7105
• DOI: 10.1097/FJC.0000000000001133
• Languages: English
• ISSNs: 0160-2446

Abstract

Abstract : Abstract: Dexmedetomidine (DEX), an α2 -adrenoreceptor (α2 -AR) and imidazoline receptor agonist, is most often used for the sedation of patients in the intensive care unit. Its administration is associated with an increased incidence of bradycardia; however, the precise mechanism of DEX-induced bradycardia has yet to be fully elucidated. This study was undertaken to examine whether DEX modifies pacemaker activity and the underlying ionic channel function through α2 -AR and imidazoline receptors. The whole-cell patch-clamp techniques were used to record action potentials and related ionic currents of sinoatrial node cells in guinea pigs. DEX (≥10 nM) reduced sinoatrial node automaticity and the diastolic depolarization rate. DEX reduced the amplitude of hyperpolarization-activated cation current ( I f or I h ) the pacemaker current, even within the physiological pacemaker potential range. DEX slowed the I f current activation kinetics and caused a significant shift in the voltage dependence of channel activation to negative potentials. In addition, efaroxan, an α2 -AR and imidazoline I1 receptor antagonist, attenuated the inhibitory effects of DEX on sinoatrial node automaticity and I f current activity, whereas yohimbine, an α2 -AR–selective antagonist, did not. DEX did not affect the current activities of other channels, including rapidly and slowly activating delayed rectifier K + currents ( I Kr and I Ks ), L-type Ca 2+ current ( I Ca, L ), Na + /Ca 2+ exchange current ( I NCX ), and muscarinic K + current ( I K, ACh ). Our results indicate that DEX, at clinically relevant concentrations, induced a negative chronotropic effect on the sinoatrial node function through the downregulation of I f current through an imidazoline I1 receptor other than the α2 -AR in the clinical setting. Abstract : Supplemental Digital Content is Available in the Text.