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


CONCLUSIONS
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.
Cheng
Hui-Wen
HW
Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai, China.
Yang
Hong-Tian
HT
Zhou
Jing-Jing
JJ
Ji
Yong-Hua
YH
Zhu
Hong-Yan
HY
D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects; D001703:Biophysics; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D000077212:Ropivacaine; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D014982:Xenopus laevis
D000577:Amides; D000779:Anesthetics, Local; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; C568322:Scn5a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D000077212:Ropivacaine