| Protein tyrosine kinase-dependent modulation of isoflurane effects on cardiac sarcolemmal K(ATP) channel. | |
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MedLine Citation:
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PMID: 12411806 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Cardiac adenosine triphosphate-sensitive potassium (K(ATP)) channels and protein tyrosine kinases (PTKs) are mediators of ischemic preconditioning, but the interaction of both and a role in myocardial protection afforded by volatile anesthetics have not been defined. METHODS: Whole cell and single channel patch clamp techniques were used to investigate the effects of isoflurane and the PTK inhibitor genistein on the cardiac sarcolemmal K(ATP) channel in acutely dissociated guinea pig ventricular myocytes. RESULTS: At 0.5 mm internal ATP, genistein (50 microm) elicited whole cell K(ATP) current (22.5 +/- 7.9 pA/pF). Genistein effects were concentration-dependent, with an EC50 of 32.3 +/- 1.4 microm. Another PTK inhibitor, tyrphostin B42, had a similar effect. The inactive analog of genistein, daidzein (50 microm), did not elicit K(ATP) current. Isoflurane (0.5 mm) increased genistein (35 microm)-activated whole cell K(ATP) current from 14.5 +/- 3.1 to 32.5 +/- 6.6 pA/pF. Stimulation of receptor PTKs with epidermal growth factor, nerve growth factor, or insulin attenuated genistein and isoflurane effects, and the protein tyrosine phosphatase inhibitor orthovanadate (1 mm) prevented their actions on K(ATP) current. In excised inside-out membrane patches, and at fixed 0.2 mm internal ATP, genistein (50 microm) increased channel open probability from 0.053 +/- 0.016 to 0.183 +/- 0.039, but isoflurane failed to further increase open probability (0.162 +/- 0.051) of genistein-activated channels. However, applied in the presence of genistein and protein tyrosine phosphatase 1B (1 microg/ml), isoflurane significantly increased open probability to 0.473 +/- 0.114. CONCLUSIONS: These results suggest that the PTK-protein tyrosine phosphatase signaling pathway may be one of the regulators of cardiac sarcolemmal K(ATP) channel and may play a role in modulating its responsiveness to isoflurane. Relative importance of this modulation for cardioprotection by volatile anesthetics remains to be established. |
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Authors:
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Anna Stadnicka; Wai-Meng Kwok; David C Warltier; Zeljko J Bosnjak |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Anesthesiology Volume: 97 ISSN: 0003-3022 ISO Abbreviation: Anesthesiology Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-11-04 Completed Date: 2002-11-27 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 1198-208 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA. astadnic@mcw.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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pharmacology* Anesthetics, Inhalation / pharmacology* Animals Drug Synergism Female Genistein / pharmacology Guinea Pigs Heart / drug effects* Isoflurane / pharmacology* Male Potassium Channels / drug effects* Protein-Tyrosine Kinases / physiology* Sarcolemma / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL34708-14/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Inhalation; 0/Potassium Channels; 26675-46-7/Isoflurane; 446-72-0/Genistein; 56-65-5/Adenosine Triphosphate; EC 2.7.10.1/Protein-Tyrosine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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