title: Propofol increases the Ca2+ sensitivity of BKCa in the cerebral arterial smooth muscle cells of mice.
abstract: OBJECTIVE
  Propofol has the side effect of hypotension especially in the elderly and patients with hypertension. Previous studies suggest propofol-caused hypotension results from activation of large conductance Ca(2+)-sensitive K channels (BKCa). In this study, the effects of propofol on the Ca(2+) sensitivity of BKCa were investigated in mice cerebral arterial smooth muscle cells.
  
  
  METHODS
  Single smooth muscle cells were prepared from the cerebral arteries of mice. Perforated whole-cell recoding was conducted to investigate the whole-cell BKCa current and spontaneous transient outward K(+) current (STOC). Inside-out patch configuration was used to record the single channel current and to study the Ca(2+)- and voltage-dependence of BKCa.
  
  
  RESULTS
  Propofol (56 and 112 μmol/L) increased the macroscopic BKCa and STOC currents in a concentration-dependent manner. It markedly increased the total open probability (NPo) of single BKCa channel with an EC(50) value of 76 μmol/L. Furthermore, propofol significantly decreased the equilibrium dissociation constant (K(d)) of Ca(2+) for BKCa channel. The K(d) value of Ca(2+) was 0.881 μmol/L in control, and decreased to 0.694, 0.599 and 0.177 μmol/L, respectively, in the presence of propofol 28, 56 and 112 μmol/L. An analysis of the channel kinetics revealed that propofol (112 μmol/L) significantly increased the open dwell time and decreased the closed dwell time, which stabilized BKCa channel in the open state.
  
  
  CONCLUSIONS
  Propofol increases the Ca(2+) sensitivity of BKCa channels, thus lowering the Ca(2+) threshold of the channel activation in arterial smooth muscle cells, which causes greater vasodilating effects.
authors.affiliation: Anesthesiology Department of Affiliated Hospital of Luzhou Medical College, China.
authors.forename: Xue-ru
authors.initials: XR
authors.lastname: Liu
authors.forename: Xiao-qiu
authors.initials: XQ
authors.lastname: Tan
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiao-rong
authors.initials: XR
authors.lastname: Zeng
authors.forename: Xian-ling
authors.initials: XL
authors.lastname: Tang
mesh_terms: D018686:Anesthetics, Intravenous; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002536:Cerebral Arteries / Q000033:anatomy & histology*; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology
chemical_list: D018686:Anesthetics, Intravenous; D024681:Potassium Channels, Calcium-Activated; D002118:Calcium; D015742:Propofol
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