Pharmacological modulation of brain Nav1.2 and cardiac Nav1.5 subtypes by the local anesthetic ropivacaine

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 patchclamp 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. © 2010 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg.