Ionic mechanisms of the action of anaesthetics on sinoatrial node automaticity.

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Kojima A, Matsuura H

Ionic mechanisms of the action of anaesthetics on sinoatrial node automaticity.

Eur J Pharmacol. 2017 Nov 5;814:63-72. doi: 10.1016/j.ejphar.2017.08.006. Epub 2017 Aug 9.

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28800884 [ View in PubMed
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Abstract

Although various general anaesthetics affect the heart rate in clinical settings, their precise mechanisms remain to be fully elucidated. Because the heart rate is determined by automaticity of the cardiac pacemaker sinoatrial node and its regulation by autonomic nervous system, it is important to clarify the effect of anaesthetics on sinoatrial node automaticity. The spontaneous electrical activity of sinoatrial node is generated by a complex but coordinated interaction of multiple ionic currents, such as the hyperpolarisation-activated cation current (If), T-type and L-type Ca(2+) currents (ICa,T and ICa,L), Na(+)/Ca(2+) exchange current (INCX), and rapidly and slowly activating delayed rectifier K(+) currents (IKr and IKs). Patch-clamp studies have revealed the direct inhibitory effects of various anaesthetics on sinoatrial node automaticity and its underlying ionic mechanisms. Sevoflurane, desflurane and propofol directly suppress the sinoatrial node automaticity by inhibiting multiple ionic channels and transporter, such as If, ICa,T, ICa,L, IKs and INCX. By incorporating these inhibitory effects of anaesthetics on multiple ion channels and transporter into sinoatrial node model, suppression of sinoatrial node activity is well reproduced in computer simulation. The inhibitory effect of anaesthetics on sinoatrial node automaticity can be exaggerated under some pathophysiological conditions, such as aging, heart failure and arrhythmias, where the function and/or expression of ion channels involved in sinoatrial node automaticity are modulated. This review focuses on molecular, ionic and cellular mechanisms underlying the regulation of sinoatrial node automaticity by anaesthetics, which will provide an electrophysiological and molecular basis for understanding the changes in heart rate during perioperative period.

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