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 μmol/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). Conclusion: Only (S)-Aml has calcium channel blockade activity, while (R)-Aml has none of the pharmacologic actions associated with CCBs.