The anesthetic bupivacaine induces cardiotoxicity by targeting L-type voltage-dependent calcium channels

Abstract

Objective: Bupivacaine is an amide local anesthetic with possible side effects that include an irregular heart rate. However, the mechanism of bupivacaine-induced cardiotoxicity has not been fully elucidated, thus we aimed to examine this mechanism. Methods: We performed electrocardiogram recordings to detect action potential waveforms in Sprague Dawley rats after application of bupivacaine, while calcium (Ca2+) currents in neonatal rat ventricular cells were examined by patch clamp recording. Western blot and quantitative real-time polymerase chain reaction assays were used to detect the expression levels of targets of interest. Results: In the present study, after application of bupivacaine, abnormal action potential waveforms were detected in Sprague Dawley rats by electrocardiogram recordings, while decreased Ca2+ currents were confirmed in neonatal rat ventricular cells by patch clamp recording. These alterations may be attributed to a deficiency of CaV1.3 (L-type) Ca2+ channels, which may be regulated by the multifunctional protein calreticulin. Conclusions: The present study identifies a possible role of the calreticulin–CaV1.3 axis in bupivacaine-induced abnormal action potentials and Ca2+ currents, which may lead to a better understanding anesthetic drug-induced cardiotoxicity.