Effects of (S)-amlodipine and (R)-amlodipine on L-type calcium channel current of rat ventricular myocytes and cytosolic calcium of aortic smooth muscle cells.
OBJECTIVE
Amlodipine (Aml) has R- and S-isomers with different pharmacological effects. However, no data are available on the influence of (S)-Aml and (R)-Aml on L-type calcium channel current (I(Ca-L)) or cytosolic calcium (Ca2+). This study is to investigate effects on I(Ca-L) and cytosolic Ca2+.


METHODS
I(Ca-L), peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with (S)-Aml and (R)-Aml were recorded by whole-cell patch clamp configuration. Cytosolic Ca2+ of smooth muscle cells was assayed by Fura-2/AM.


RESULTS
At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, 1.5 +/- 0.2%, 25.4 +/- 5.3%, 65.2 +/- 7.3%, 78.4 +/- 8.1%, and 94.2 +/- 5.0% of I(Ca-L) were blocked by (S)-Aml. I-V curves were shifted upward. Half-activation voltages were -16.01 +/- 1.65 mV, -17.61 +/- 1.60 mV, -20.17 +/- 1.46 mV, -21.87 +/- 1.69 mV and -24.09 +/- 1.87 mV (P < 0.05). Half-inactivation voltages were -27.16 +/- 4.48 mV, -28.69 +/- 4.52 mV, -31.19 +/- 4.17 mV, -32.63 +/- 4.34 mV and -35.16 +/- 4.46 mV (P < 0.05). Recovery time were prolonged gradually (P < 0.05). 10.3 +/- 1.2%, 35.2 +/- 3.5%, 60.1 +/- 5.0%, 78.9 +/- 6.1%, and 91.2 +/- 7.6% of cytosolic Ca2+ were reduced at different concentrations (P < 0.05). However, (R)-Aml at different concentrations had no effect on I(Ca-L) and cytosolic Ca2+ (P > 0.05).


CONCLUSIONS
Only (S)-Aml has calcium channel blockade activity, while (R)-Aml has none of the pharmacologic actions associated with CCBs.
Wang
Ru-Xing
RX
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University in Wuxi, China.
Jiang
Wen-Ping
WP
Li
Xiao-Rong
XR
Lai
Li-Hong
LH
D017311:Amlodipine / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007202:Indicators and Reagents; D012996:Solutions; D017311:Amlodipine; D002118:Calcium