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

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 (Ca) 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 Ca currents were confirmed in neonatal rat ventricular cells by patch clamp recording. These alterations may be attributed to a deficiency of Ca1.3 (L-type) Ca channels, which may be regulated by the multifunctional protein calreticulin.

CONCLUSIONS

The present study identifies a possible role of the calreticulin-Ca1.3 axis in bupivacaine-induced abnormal action potentials and Ca currents, which may lead to a better understanding anesthetic drug-induced cardiotoxicity.