Abstract
Anesthesia blocks consciousness and memory while sparing non-conscious brain activities. While the exact mechanisms of anesthetic action are unknown, the Meyer-Overton correlation provides a link between anesthetic potency and solubility in a lipid-like, non-polar medium. Anesthetic action is also related to an anesthetic's hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in lipid-like, non-polar regions within brain proteins. Generally the protein target for anesthetics is assumed to be neuronal membrane receptors and ion channels, however new evidence points to critical effects on intra-neuronal microtubules, a target of interest due to their potential role in post-operative cognitive dysfunction (POCD). Here we use binding site predictions on tubulin, the protein subunit of microtubules, with molecular docking simulations, quantum chemistry calculations, and theoretical modeling of collective dipole interactions in tubulin to investigate the effect of a group of gases including anesthetics, non-anesthetics, and anesthetic/convulsants on tubulin dynamics. We found that these gases alter collective terahertz dipole oscillations in a manner that is correlated with their anesthetic potency. Understanding anesthetic action may help reveal brain mechanisms underlying consciousness, and minimize POCD in the choice and development of anesthetics used during surgeries for patients suffering from neurodegenerative conditions with compromised cytoskeletal microtubules.
| Original language | English (US) |
|---|---|
| Article number | 9877 |
| Journal | Scientific Reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2017 |
| Externally published | Yes |
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ASJC Scopus subject areas
- General
Cite this
Anesthetic Alterations of Collective Terahertz Oscillations in Tubulin Correlate with Clinical Potency : Implications for Anesthetic Action and Post-Operative Cognitive Dysfunction. / Craddock, Travis J.A.; Kurian, Philip; Preto, Jordane; Sahu, Kamlesh; Hameroff, Stuart R; Klobukowski, Mariusz; Tuszynski, Jack A.
In: Scientific Reports, Vol. 7, No. 1, 9877, 01.12.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anesthetic Alterations of Collective Terahertz Oscillations in Tubulin Correlate with Clinical Potency
T2 - Implications for Anesthetic Action and Post-Operative Cognitive Dysfunction
AU - Craddock, Travis J.A.
AU - Kurian, Philip
AU - Preto, Jordane
AU - Sahu, Kamlesh
AU - Hameroff, Stuart R
AU - Klobukowski, Mariusz
AU - Tuszynski, Jack A.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Anesthesia blocks consciousness and memory while sparing non-conscious brain activities. While the exact mechanisms of anesthetic action are unknown, the Meyer-Overton correlation provides a link between anesthetic potency and solubility in a lipid-like, non-polar medium. Anesthetic action is also related to an anesthetic's hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in lipid-like, non-polar regions within brain proteins. Generally the protein target for anesthetics is assumed to be neuronal membrane receptors and ion channels, however new evidence points to critical effects on intra-neuronal microtubules, a target of interest due to their potential role in post-operative cognitive dysfunction (POCD). Here we use binding site predictions on tubulin, the protein subunit of microtubules, with molecular docking simulations, quantum chemistry calculations, and theoretical modeling of collective dipole interactions in tubulin to investigate the effect of a group of gases including anesthetics, non-anesthetics, and anesthetic/convulsants on tubulin dynamics. We found that these gases alter collective terahertz dipole oscillations in a manner that is correlated with their anesthetic potency. Understanding anesthetic action may help reveal brain mechanisms underlying consciousness, and minimize POCD in the choice and development of anesthetics used during surgeries for patients suffering from neurodegenerative conditions with compromised cytoskeletal microtubules.
AB - Anesthesia blocks consciousness and memory while sparing non-conscious brain activities. While the exact mechanisms of anesthetic action are unknown, the Meyer-Overton correlation provides a link between anesthetic potency and solubility in a lipid-like, non-polar medium. Anesthetic action is also related to an anesthetic's hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in lipid-like, non-polar regions within brain proteins. Generally the protein target for anesthetics is assumed to be neuronal membrane receptors and ion channels, however new evidence points to critical effects on intra-neuronal microtubules, a target of interest due to their potential role in post-operative cognitive dysfunction (POCD). Here we use binding site predictions on tubulin, the protein subunit of microtubules, with molecular docking simulations, quantum chemistry calculations, and theoretical modeling of collective dipole interactions in tubulin to investigate the effect of a group of gases including anesthetics, non-anesthetics, and anesthetic/convulsants on tubulin dynamics. We found that these gases alter collective terahertz dipole oscillations in a manner that is correlated with their anesthetic potency. Understanding anesthetic action may help reveal brain mechanisms underlying consciousness, and minimize POCD in the choice and development of anesthetics used during surgeries for patients suffering from neurodegenerative conditions with compromised cytoskeletal microtubules.
UR - http://www.scopus.com/inward/record.url?scp=85028456785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028456785&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-09992-7
DO - 10.1038/s41598-017-09992-7
M3 - Article
C2 - 28852014
AN - SCOPUS:85028456785
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 9877
ER -