Bupivacaine inhibition of L-type calcium current in ventricular cardiomyocytes of hamster.
BACKGROUND
The local anesthetic bupivacaine is cardiotoxic when accidentally injected into the circulation. Such cardiotoxicity might involve an inhibition of cardiac L-type Ca2+ current (ICa,L). This study was designed to define the mechanism of bupivacaine inhibition of ICa,L.


METHODS
Cardiomyocytes were enzymatically dispersed from hamster ventricles. Certain voltage- and time-dependencies of ICa,L were recorded using the whole-cell patch clamp method in the presence and absence of different concentrations of bupivacaine.


RESULTS
Bupivacaine, in a concentration-dependent manner (10-300 microM), tonically inhibited the peak amplitude of ICa,L. The inhibition was characterized by an increase in the time of recovery from inactivation and a negative-voltage shift of the steady-state inactivation curve. The inhibition was shown to be voltage-dependent, and the peak amplitude of ICa,L could not be restored to control levels by a wash from bupivacaine.


CONCLUSIONS
The inhibition of ICa,L appears, in part, to result from bupivacaine predisposing L-type Ca channels to the inactivated state. Data from washout suggest that there may be two mechanisms of inhibition at work. Bupivacaine may bind with low affinity to the Ca channel and also affect an unidentified metabolic component that modulates Ca channel function.
Rossner
K L
KL
Department of Anesthesiology, Winthrop-University Hospital, Mineola, New York, USA. krossner@epo.som.sunysb.edu
Freese
K J
KJ
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D020746:Calcium Channels, L-Type; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D008297:Male
D000779:Anesthetics, Local; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002045:Bupivacaine