[Effects of different amlodipine isomers on L-type calcium current of rat ventricular myocytes].
OBJECTIVE
To investigate the effects of different amlodipine isomers on L-type calcium current (ICa-L) and kinetics of rat ventricular myocytes.


METHODS
Rat ventricular myocytes were isolated by enzyme digestion. ICa-L, peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with S-amlodipine, R-amlodipine and R, S-amlodipine at concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L were recorded by whole-cell patch clamp configuration.


RESULTS
At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, ICa-L were blocked in a dose-dependent manner by S-amlodipine [(1.5 +/- 0.2)%, (25.4 +/- 5.3)%, (65.2 +/- 7.3)%, (78.4 +/- 8.1)%, and (94.2 +/- 5.0)%] and by R, S-amlodipine [(0.9 +/- 0.1)%, (10.4 +/- 3.2)%, (69.1 +/- 5.3)%, (75.2 +/- 7.0)%, and (81.6 +/- 6.4)%]. I-V curves were significantly shifted upward, steady state activation and inactivation curves were significantly shifted to left by S-amlodipine and R, S-amlodipine (0.1 micromol/L to 10 micromol/L). Recovery time from inactivation was also significantly prolonged by S-amlodipine [(210.1 +/- 19.5) ms, (225.2 +/- 21.3) ms, (241.7 +/- 20.3) ms, (252.3 +/- 24.2) ms, and (282.6 +/- 23.2) ms] and by R, S-amlodipine [(208.7 +/- 17.4) ms, (215.8 +/- 18.3) ms, (225.2 +/- 21.3) ms, (235.8 +/- 22.7) ms, and (252.3 +/- 24.2) ms] in a dose-dependent manner. The observed effects of S-amlodipine were more potent than those of R, S-amlodipine (P < 0.05). However, all these parameters were not affected by R-amlodipine at various concentrations (P > 0.05).


CONCLUSIONS
L-type calcium current of rat ventricular myocytes could be blocked by R, S-amlodipine and S-amlodipine in a dose-dependent manner.
Wang
Ru-xing
RX
Department of Cardiology, First Affiliated Hospital of Suzhou University, Suzhou 215006, China.
Song
Jian-ping
JP
Yang
Xiang-jun
XJ
Liu
Zhi-hua
ZH
Jiang
Ting-bo
TB
Li
Hong-xia
HX
Zhou
Lin
L
Li
Xiao-rong
XR
Jiang
Wen-ping
WP
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D017311:Amlodipine