title: Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart.
abstract: OBJECTIVE
  The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms.
  
  
  METHODS
  Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (I(f) ), T-type and L-type Ca²⁺ currents (I(Ca,T) and I(Ca,L) , respectively), and slowly activating delayed rectifier K⁺ current (I(Ks) ), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation.
  
  
  RESULTS
  In isolated SA node cells, sevoflurane (0.12-0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased I(f) , I(Ca,T) , I(Ca,L) and I(Ks) by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs.
  
  
  CONCLUSIONS
  Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on I(f) , I(Ca,T) and I(Ca,L) . These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings.
authors.affiliation: Department of Anesthesiology, Shiga University of Medical Science, Otsu, Shiga, Japan. akiko77@belle.shiga-med.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Kojima
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Omatsu-Kanbe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Nosaka
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D000077149:Sevoflurane; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane