Open AccessPotent Inactivation-Dependent Inhibition of Adult and Neonatal NaV1.5 Channels by Lidocaine and Levobupivacaine
Author(s) -
Taha Elajnaf,
Daniel T. BaptistaHon,
Tim G. Hales
Publication year - 2018
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/ane.0000000000003597
Subject(s) - levobupivacaine , medicine , nav1 , lidocaine , anesthesia , pharmacology , sodium channel , bupivacaine , chemistry , organic chemistry , sodium
Cardiotoxic effects of local anesthetics (LAs) involve inhibition of NaV1.5 voltage-gated Na channels. Metastatic breast and colon cancer cells also express NaV1.5, predominantly the neonatal splice variant (nNaV1.5) and their inhibition by LAs reduces invasion and migration. It may be advantageous to target cancer cells while sparing cardiac function through selective blockade of nNaV1.5 and/or by preferentially affecting inactivated NaV1.5, which predominate in cancer cells. We tested the hypotheses that lidocaine and levobupivacaine differentially affect (1) adult (aNaV1.5) and nNaV1.5 and (2) the resting and inactivated states of NaV1.5.