title: 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 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.
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai, China.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Cheng
authors.forename: Hong-Tian
authors.initials: HT
authors.lastname: Yang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhou
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Ji
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhu
mesh_terms: 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
chemical_list: 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