PMID- 12573994
OWN - NLM
STAT- MEDLINE
DCOM- 20030515
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 284
IP  - 5
DP  - 2003 May
TI  - Isoflurane activates rat mitochondrial ATP-sensitive K+ channels reconstituted in 
      lipid bilayers.
PG  - H1865-71
AB  - Activation of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels is critical 
      in myocardial protection induced by preconditioning with volatile anesthetics or 
      brief periods of ischemia. In this study, we characterized rat mitoK(ATP) 
      channels reconstituted in lipid bilayers and examined their direct regulation by 
      isoflurane. Mitochondria and the inner membrane fraction were isolated from rat 
      ventricles and fused into lipid bilayers. On the basis of their inhibition by 
      5-hydroxydecanoate (5-HD)/ATP or activation by diazoxide, mitoK(ATP) channels of 
      several conductance states were observed in symmetrical (150 mM) potassium 
      glutamate (26, 47, 66, 83, and 105 pS). Isoflurane (0.8 mM) increased the 
      cumulative open probability from 0.09 +/- 0.02 at baseline to 0.50 +/- 0.09 (P < 
      0.05, n = 5), which was inhibited by 5-HD. Isoflurane caused a dose-dependent 
      rightward shift in ATP inhibition of mitoK(ATP) channels, which increased the 
      IC(50) for ATP from 335 +/- 4 to 940 +/- 34 microM at 0.8 mM (P < 0.05, n = 5 
      approximately 8). We conclude that direct activation of the mitoK(ATP) channel by 
      isoflurane is likely to contribute to volatile anesthetic-induced myocardial 
      preconditioning.
FAU - Nakae, Yuri
AU  - Nakae Y
AD  - Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank 
      Road, Milwaukee, WI 53226, USA.
FAU - Kwok, Wai-Meng
AU  - Kwok WM
FAU - Bosnjak, Zeljko J
AU  - Bosnjak ZJ
FAU - Jiang, Ming Tao
AU  - Jiang MT
LA  - eng
GR  - HL 34708/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030206
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Lipid Bilayers)
RN  - 0 (Potassium Channels)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Anesthetics, Inhalation/*pharmacology
MH  - Animals
MH  - Ischemic Preconditioning, Myocardial
MH  - Isoflurane/*pharmacology
MH  - Lipid Bilayers/metabolism
MH  - Mitochondria/*drug effects/*metabolism
MH  - Myocardium/metabolism
MH  - Potassium Channels/*metabolism
MH  - Rats
EDAT- 2003/02/08 04:00
MHDA- 2003/05/16 05:00
CRDT- 2003/02/08 04:00
PHST- 2003/02/08 04:00 [pubmed]
PHST- 2003/05/16 05:00 [medline]
PHST- 2003/02/08 04:00 [entrez]
AID - 01031.2002 [pii]
AID - 10.1152/ajpheart.01031.2002 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1865-71. doi: 
      10.1152/ajpheart.01031.2002. Epub 2003 Feb 6.