Pharmacological Modulation of Brain Nav1.2 and Cardiac Nav1.5 Subtypes by the Local Anesthetic Ropivacaine

Overview

Journal Neurosci Bull

Specialty Neurology

Date 2010 Jul 24

PMID 20651810

Citations 2

Authors

Hui-Wen Cheng

Hong-Tian Yang

Jing-Jing Zhou

Yong-Hua Ji

Hong-Yan Zhu

Affiliations

Soon will be listed here.

Abstract

Objective: The present study was aimed to investigate the pharmacological modulatory effects of ropivacaine, an amide-type local anesthetic, on rat Nav1.2 (rNav1.2) and rNav1.5, the two Na(+) channel isoforms heterologously expressed in Xenopus oocytes and in HEK293t cell line, respectively.

Methods: Two-electrode voltage-clamp (TEVC) and whole-cell patch-clamp recordings were employed to record the whole-cell currents.

Results: Ropivacaine induced tonic inhibition of peak Na(+) currents of both subtypes in a dose- and frequency-dependent manner. rNav1.5 appeared to be more sensitive to ropivacaine. In addition, for both Na(+) channel subtypes, the steady-state inactivation curves, but not the activation curves, were significantly shifted to the hyperpolarizing direction by ropivacaine. Use-dependent blockade of both rNav1.2 and rNav1.5 channels was induced by ropivacaine through a high frequency of depolarization, suggesting that ropivacaine could preferentially bind to the 2 inactivated Na(+) channel isoforms.

Conclusion: The results will be helpful in understanding the pharmacological modulation by ropivacaine on Nav1.2 subtype in the central nervous system, and on Nav1.5 subtype abundantly expressed in the heart.

Citing Articles

Tetrodotoxin-sensitive α-subunits of voltage-gated sodium channels are relevant for inhibition of cardiac sodium currents by local anesthetics.

Stoetzer C, Doll T, Stueber T, Herzog C, Echtermeyer F, Greulich F Naunyn Schmiedebergs Arch Pharmacol. 2016; 389(6):625-36.

PMID: 27000037 DOI: 10.1007/s00210-016-1231-9.

Voltage-dependent blockade by bupivacaine of cardiac sodium channels expressed in Xenopus oocytes.

Zhang H, Ji H, Liu Z, Ji Y, You X, Ding G Neurosci Bull. 2014; 30(4):697-710.

PMID: 25008571 PMC: 5562622. DOI: 10.1007/s12264-013-1449-1.

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