@article{APS9269,
author = {An-tao LUO and Zhen-zhen CAO and Yu XIANG and Shuo ZHANG and Chun-ping QIAN and Chen FU and Pei-hua ZHANG, and Ji-hua MA},
title = {Ketamine attenuates the Na + -dependent Ca 2+ overload in rabbit ventricular myocytes in vitro by inhibiting late Na + and L-type Ca 2+ currents},
journal = {Acta Pharmacologica Sinica},
volume = {36},
number = {11},
year = {2017},
keywords = {},
abstract = {Aim: Intracellular Ca2+ ([Ca2+]i) overload occurs in myocardial ischemia. An increase in the late sodium current (INaL) causes intracellular Na+ overload and subsequently [Ca2+]i overload via the reverse-mode sodium-calcium exchanger (NCX). Thus, inhibition of INaL is a potential therapeutic target for cardiac diseases associated with [Ca2+]i overload. The aim of this study was to investigate the effects of ketamine on Na+-dependent Ca2+ overload in ventricular myocytes in vitro.
Methods: Ventricular myocytes were enzymatically isolated from hearts of rabbits. INaL, NCX current (INCX) and L-type Ca2+ current (ICaL) were recorded using whole-cell patch-clamp technique. Myocyte shortening and [Ca2+]i transients were measured simultaneously using a video-based edge detection and dual excitation fluorescence photomultiplier system.
Results: Ketamine (20, 40, 80 μmol/L) inhibited INaL in a concentration-dependent manner. In the presence of sea anemone toxin II (ATX, 30 nmol/L), INaL was augmented by more than 3-fold, while ketamine concentration-dependently suppressed the ATX-augmented INaL. Ketamine (40 μmol/L) also significantly suppressed hypoxia or H2O2-induced enhancement of INaL. Furthermore, ketamine concentration-dependently attenuated ATX-induced enhancement of reverse-mode INCX. In addition, ketamine (40 μmol/L) inhibited ICaL by 33.4%. In the presence of ATX (3 nmol/L), the rate and amplitude of cell shortening and relaxation, the diastolic [Ca2+]i, and the rate and amplitude of [Ca2+]i rise and decay were significantly increased, which were reverted to control levels by tetrodotoxin (TTX, 2 μmol/L) or by ketamine (40 μmol/L).
Conclusion: Ketamine protects isolated rabbit ventricular myocytes against [Ca2+]i overload by inhibiting INaL and ICaL.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9269}
}