Journal article
Ketamine, at Clinical Concentrations, Does Not Alter the Function of Cardiac Sarcoplasmic Reticulum Calcium Release Channels
Anesthesia and analgesia, Vol.81(4), pp.849-854
10/1995
DOI: 10.1097/00000539-199510000-00033
PMID: 7574022
Abstract
In the absence of sympathetically mediated stimulation, ketamine depresses myocardial contractility.This results from a decrease in the availability of intracellular Ca for excitation-contraction coupling. Although sites of action other than the Ca release channel of sarcoplasmic reticulum have been implicated, ketamine-induced alterations in Ca efflux from the sarcoplasmic reticulum remain contentious. The purpose of the present study was to identify interactions of ketamine with the calcium release channel using sarcoplasmic reticulum enriched vesicles from porcine left ventricle. Ketamine did not alter [() H]ryanodine binding at concentrations of 1 mM or less, while binding was almost completely inhibited at 10 mM. Gating and conductance of SR Ca channels studied in planar bilayers was not altered by clinical concentrations of ketamine over the range of physiologic cytoplasmic free Ca concentrations. Channel inactivation was observed at 10 mM ketamine, well in excess of clinical concentrations. These findings indicate that clinical concentrations of ketamine do not alter the function of the Ca release channel. Alterations in intracellular Ca homeostasis that result in depression of myocardial contractility must therefore result from effects at other sites along the excitation-contraction coupling pathway.(Anesth Analg 1995;81:849-54)
Details
- Title: Subtitle
- Ketamine, at Clinical Concentrations, Does Not Alter the Function of Cardiac Sarcoplasmic Reticulum Calcium Release Channels
- Creators
- Timothy J Connelly - Departments of Anesthesiology (Connelly, Ahern) and Physiology, University of Wisconsin-Madison, and the William S. Middleton Veterans Administration Hospital, Madison, Wisconsin (Coronado). This work was supported by a Young Investigator Award from the Foundation for Anesthesia Education and Research and the Society of Cardiovascular Anesthesiologists, a B. B. Sankey Award from the International Anesthesia Research Society and a Research Starter Grant from the Pharmaceutical Manufacturers Association Foundation. Accepted for publication May 15, 1995. Address correspondence to Timothy J. Connelly, MD, B6/319 Clinical Science Center, 600 Highland Ave., Madison, WI 53792Christopher AhernRoberto Coronado
- Resource Type
- Journal article
- Publication Details
- Anesthesia and analgesia, Vol.81(4), pp.849-854
- Publisher
- International Anesthesia Research Society
- DOI
- 10.1097/00000539-199510000-00033
- PMID
- 7574022
- ISSN
- 0003-2999
- eISSN
- 1526-7598
- Language
- English
- Date published
- 10/1995
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984070723302771
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