QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ouyang, W. Articles by Hemmings, H. C. Search for Related Content PubMed PubMed Citation Articles by Ouyang, W. Articles by Hemmings, H. C., Jr

Isoflurane and Propofol Inhibit Voltage-Gated Sodium Channels in Isolated Rat Neurohypophysial Nerve Terminals

Departments of Anesthesiology (W.O., H.C.H.), Neurology and Neuroscience (G.W.), and Pharmacology (H.C.H.), Weill Medical College of Cornell University, New York, New York

Mounting electrophysiological evidence indicates that certain general anesthetics, volatile anesthetics in particular, depress excitatory synaptic transmission by presynaptic mechanisms. We studied the effects of representative general anesthetics on voltage-gated Na⁺ currents (I_Na) in nerve terminals isolated from rat neurohypophysis using patch-clamp electrophysiological analysis. Both isoflurane and propofol inhibited I_Na in a dose-dependent and reversible manner. At holding potentials of -70 or -90 mV, isoflurane inhibited peak I_Na with IC₅₀ values of 0.45 and 0.56 mM, and propofol inhibited peak I_Na with IC₅₀ values of 4.1 and 6.0 µM, respectively. Isoflurane (0.8 mM) did not significantly alter the V_1/2 of activation; propofol caused a small positive shift. Isoflurane (0.8 mM) or propofol (5 µM) produced a negative shift in the voltage dependence of inactivation. Recovery of I_Na from inactivation was slower from a holding potential of -70 mV than from -90 mV; isoflurane and propofol further delayed recovery from inactivation. In conclusion, the volatile anesthetic isoflurane and the intravenous anesthetic propofol inhibit voltage-gated Na⁺ currents in isolated neurohypophysial nerve terminals in a concentration- and voltage-dependent manner. Marked effects on the voltage dependence and kinetics of inactivation and minimal effects on activation support preferential anesthetic interactions with the fast inactivated state of the Na⁺ channel. These results are consistent with direct inhibition of oxytocin and vasopressin release from the neurohypophysis by isoflurane and propofol. Inhibition of voltage-gated Na⁺ channels may contribute to the presynaptic effects of general anesthetics on nerve terminal excitability and neurotransmitter release.

Address correspondence to: Dr. Hugh C Hemmings, Jr., Department of Anesthesiology, Box 50, LC-203, 525 E. 68th St., Weill Medical College of Cornell University, New York, NY 10021. E-mail: hchemmi{at}med.cornell.edu

This article has been cited by other articles:

				E. I. Eger II, D. E. Raines, S. L. Shafer, H. C. Hemmings Jr, and J. M. Sonner Is a New Paradigm Needed to Explain How Inhaled Anesthetics Produce Immobility? Anesth. Analg., September 1, 2008; 107(3): 832 - 848. [Abstract] [Full Text] [PDF]

				T. Horishita and R. A. Harris n-Alcohols Inhibit Voltage-Gated Na+ Channels Expressed in Xenopus Oocytes J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 270 - 277. [Abstract] [Full Text] [PDF]

				C. C. Chu, S. Z. Wu, W. L. Su, J. P. Shieh, C. H. Kao, S. T. Ho, and J. J. Wang Subcutaneous injection of inhaled anesthetics produces cutaneous analgesia: [L'injection sous-cutanee d'agents anesthesiques volatils genere une analgesie cutanee] Can J Anesth, May 1, 2008; 55(5): 290 - 294. [Abstract] [Full Text] [PDF]

				W. Ouyang, T.-Y. Jih, T.-T. Zhang, A. M. Correa, and H. C. Hemmings Jr. Isoflurane Inhibits NaChBac, a Prokaryotic Voltage-Gated Sodium Channel J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1076 - 1083. [Abstract] [Full Text] [PDF]

				M. J. Laster, Y. Zhang, E. I. Eger II, D. Shnayderman, and J. M. Sonner Alterations in Spinal, but Not Cerebral, Cerebrospinal Fluid Na+ Concentrations Affect the Isoflurane Minimum Alveolar Concentration in Rats Anesth. Analg., September 1, 2007; 105(3): 661 - 665. [Abstract] [Full Text] [PDF]

				C. E. Morris and P. F. Juranka Nav Channel Mechanosensitivity: Activation and Inactivation Accelerate Reversibly with Stretch Biophys. J., August 1, 2007; 93(3): 822 - 833. [Abstract] [Full Text] [PDF]

				R. I. Westphalen and H. C. Hemmings Jr. Volatile Anesthetic Effects on Glutamate versus GABA Release from Isolated Rat Cortical Nerve Terminals: 4-Aminopyridine-Evoked Release J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 216 - 223. [Abstract] [Full Text] [PDF]

				H. C. Hemmings Jr., W. Yan, R. I. Westphalen, and T. A. Ryan The General Anesthetic Isoflurane Depresses Synaptic Vesicle Exocytosis Mol. Pharmacol., May 1, 2005; 67(5): 1591 - 1599. [Abstract] [Full Text] [PDF]

				W. Ouyang and H. C. Hemmings Jr. Depression by Isoflurane of the Action Potential and Underlying Voltage-Gated Ion Currents in Isolated Rat Neurohypophysial Nerve Terminals J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 801 - 808. [Abstract] [Full Text] [PDF]

				M. Shiraishi and R. A. Harris Effects of Alcohols and Anesthetics on Recombinant Voltage-Gated Na+ Channels J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 987 - 994. [Abstract] [Full Text] [PDF]