Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Wiley full text link Wiley Free PMC article
Full text links

Actions

Share

.2010 Feb;159(4):872-8.
doi: 10.1111/j.1476-5381.2009.00583.x. Epub 2010 Jan 25.

Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats

Affiliations

Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats

Y Zhang et al. Br J Pharmacol.2010 Feb.

Abstract

Background and purpose: Results from several studies point to voltage-gated Na(+) channels as potential mediators of the immobility produced by inhaled anaesthetics. We hypothesized that the intrathecal administration of tetrodotoxin, a drug that blocks Na(+) channels, should enhance anaesthetic potency, and that concurrent administration of veratridine, a drug that augments Na(+) channel opening, should reverse the increase in potency.

Experimental approach: We measured the change in isoflurane potency for reducing movement in response to a painful stimulus as defined by MAC (minimum alveolar concentration of anaesthetic required to abolish movement in 50% of subjects) caused by intrathecal infusion of various concentrations of tetrodotoxin into the lumbothoracic subarachnoid space of rats, and the change in MAC caused by the administration of a fixed dose of tetrodotoxin plus various doses of intrathecal veratridine.

Key results: Intrathecal infusion of tetrodotoxin (0.078-0.63 microM) produced a reversible dose-related decrease in MAC, of more than 50% at the highest concentration. Intrathecal co-administration of veratridine (1.6-6.4 microM) reversed this decrease in a dose-related manner, with nearly complete reversal at the highest veratridine dose tested.

Conclusions and implications: Intrathecal administration of tetrodotoxin increases isoflurane potency (decreases isoflurane MAC), and intrathecal administration of veratridine counteracts this effect in vivo. These findings are consistent with a role for voltage-gated Na(+) channel blockade in the immobility produced by inhaled anaesthetics.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representations of the experimental design for the two studies: (i) effect on MAC of various concentrations of intrathecal tetrodotoxin infused for 30 min (tetrodotoxin alone); and (ii) capacity of various concentrations of intrathecal veratridine to antagonize the reduction in MAC produced by 0.47 µM tetrodotoxin infused intrathecally for 30 min before infusion of various concentrations of intrathecal veratridine (tetrodotoxin plus veratridine). aCSF, artificial cerebrospinal fluid; MAC, minimum alveolar concentration of anaesthetic required to abolish movement in 50% of subjects.
Figure 2
Figure 2
Intrathecal infusion of tetrodotoxin alone decreased isoflurane MAC (minimum alveolar concentration of anaesthetic required to abolish movement in 50% of subjects). The effect of tetrodotoxin on MAC (MAC1/MAC0) was dose-related as indicated by non-linear curve fitting of the data with variable slope. The IC50 value for the infusion was 0.33 µM tetrodotoxin with a best fit plateau at a MAC ratio of 0.36 (Hill slope =−6.4). This effect was reversible with subsequent recovery of MAC to control values 24 h after cessation of tetrodotoxin infusion (MAC2/MAC0). Data are shown as mean ± SD (n= 4–6 rats for each concentration).
Figure 3
Figure 3
Intrathecal veratridine reversed the reduction in isoflurane MAC (minimum alveolar concentration of anaesthetic required to abolish movement in 50% of subjects) produced by intrathecal tetrodotoxin. Intrathecal infusion of 0.47 µM tetrodotoxin decreased isoflurane MAC (MAC1/MAC0) to 35 ± 4% of control. Infusion of veratridine at all three concentrations reversed the effect of the tetrodotoxin (MAC1′/MAC0;P < 0.0001 byanova with Dunnett's multiple comparison test). Data shown are mean ± SD (n= 4–6 rats for each concentration).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alexander SPH, Mathie A, Peters JA. Guide to receptors and channels (GRAC), 3rd edition (2008 revision) Br J Pharmacol. 2008;153(Suppl. 2):S1–S209. - PMC - PubMed
    1. Antognini JF, Schwartz K. Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology. 1993;79:1244–1249. - PubMed
    1. Banasiak KJ, Burenkova O, Haddad GG. Activation of voltage-sensitive sodium channels during oxygen deprivation leads to apoptotic neuronal death. Neuroscience. 2004;126:31–44. - PubMed
    1. Borison HL, McCarthy LE. Respiratory and circulatory effects of saxitoxin in the cerebrospinal fluid. Br J Pharmacol. 1977;61:679–689. - PMC - PubMed
    1. Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T. Voltage-gated ion channels and gating modifier toxins. Toxicon. 2007;49:124–141. - PubMed

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full text links
Wiley full text link Wiley Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp