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BACKGROUND:

Cardiotoxic effects of local anesthetics (LAs) involve inhibition of Na V 1.5 voltage-gated Na+ channels. Metastatic breast and colon cancer cells also express Na V 1.5, predominantly the neonatal splice variant (nNa V 1.5) 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 nNa V 1.5 and/or by preferentially affecting inactivated Na V 1.5, which predominate in cancer cells. We tested the hypotheses that lidocaine and levobupivacaine differentially affect (1) adult (aNa V 1.5) and nNa V 1.5 and (2) the resting and inactivated states of Na V 1.5.

METHODS:

The whole-cell voltage-clamp technique was used to evaluate the actions of lidocaine and levobupivacaine on recombinant Na V 1.5 channels expressed in HEK-293 cells. Cells were transiently transfected with cDNAs encoding either …