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Effects of intravenous and local anesthetic agents on -conotoxin MVII_A binding to rat cerebrocortex

Kazuyoshi Hirota, MD^*, and David G. Lambert, PhD

^* From the University Department of Anaesthesia and Pain Management, Leicester Royal Infirmary,
Leicester LE1 5WW, UK, and Department of Anesthesiology University of Hirosaki School of Medicine, Hirosaki, Japan.

Address correspondence to: Dr. D.G. Lambert. Phone: +44-116-258-5291; Fax: +44-116-285-4487; E-mail: DGL3{at}le.ac.uk

Purpose: The cellular target site(s) for anesthetic action remain controversial. In this study we have examined any interaction of iv anesthetics (thiopental, pentobarbital, ketamine, etomidate, propofol, alphaxalone), local anesthetics (lidocaine, prilocaine, procaine and tetracaine), and the non anesthetic barbiturate, barbituric acid with the -conotoxin MVII_A binding site on N-type voltage sensitive Ca²⁺ channels in rat cerebrocortical membranes.

Methods: [¹²⁵I] -conotoxin MVII_A binding assays were performed in 0.5 ml volumes of Tris.HCl buffer containing BSA 0.1% for 30 min at 20°C using fresh cerebrocortical membranes (5 µg of protein). Non-specific binding was defined in the presence of excess (10^–8 M) -conotoxin MVII_A. The interaction of iv (alphaxolone, etomidate, propofol, pentobarbitone, ketamine and thiopentone), local (lidocaine, prilocaine, procaine and tetracaine) anesthetics and barbituric acid was determined by displacement of [¹²⁵I] -conotoxin MVII_A (~1pM).

Results: The binding of [¹²⁵I] -conotoxin was concentration-dependent and saturable with B_max and K_d of 223 ± 15 fmol/mg protein and 2.13 ± 0.14 pM, respectively. Unlabelled -conotoxin MVII_A displaced [¹²⁵I] -conotoxin MVII_A yielding a pK_d of 11.04 ± 0.04 (9.2 pM). All iv and local anesthetics at clinically relevant concentrations did not show any interaction with the -conotoxin MVII_A binding site.

Conclusion: The present study suggests that -conotoxin MVII_A binding site on N-type voltage sensitive Ca²⁺ channels may not be a target for iv and local anesthetic agents.

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