Characteristics of L-type calcium channel blockade by lacidipine in guinea-pig ventricular myocytes |
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Authors: | Elisabetta Cerbai Alberto Giotti Alessandro Mugelli |
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Institution: | Department of Pharmacology, University of Firenze, Italy |
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Abstract: | - The Ca2+-antagonistic properties of lacidipine were investigated in patch-clamp guinea-pig ventricular myocytes.
- In basal conditions, 0.1 μM lacidipine reduced the action potential duration, associated with a decrease in the L-type calcium current (ICa,L) to 66±4% of the control value, without a change in the current-voltage relationship. Sodium current and background potassium currents were not affected. All the effects reached a steady state within 2 min.
- The Ca2+-antagonistic effect of lacidipine was voltage-dependent: a marked negative shift (about 20 mV) of the steady-state inactivation curve was observed with long (10 s) conditioning prepulses, but not with short (350 ms) prepulses.
- The onset of and recovery from the voltage-dependent effect caused by 0.1 μM lacidipine were significantly slower when compared to those of equiactive concentrations of nimodipine (0.5 μM) and nisoldipine (0.1 μM). ICa,L measured after prepulses at −40 mV lasting 500 ms or less was unchanged (95±5% of maximum current value) while it was reduced to 49±10% by nimodipine and 43±9% by nisoldipine (P<0.05 vs lacidipine for both).
- Similarly, the recovery from block in the presence of lacidipine was slower than with nimodipine and nisoldipine. After a prepulse of 1 s at −80 mV, ICa,L recovered up to 54±2% of the maximum current value in the presence of lacidipine, and up to 91±3% and 93±5% in the presence of nimodipine and nisoldipine, respectively (P<0.05 vs lacidipine).
- Blockade of ICa,L by lacidipine was use-dependent. After ten 200 ms long pulses (1 Hz) from −80 mV, ICa,L was reduced to 55±7% of the current measured at the first pulse. In the presence of nimodipine and nisoldipine, ICa,L elicited by the tenth pulse amounted to 93±3% and 80±6% of the first pulse value, respectively (P<0.05 vs lacidipine). Lacidipine did not cause use-dependent blockade of ICa,L in cells stimulated with 10 ms long pulses.
- These results demonstrate that lacidipine selectively inhibits ICa,L in isolated cardiomyocytes and suggest that this effect occurs mainly through binding to the inactivated Ca2+ channels.
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Keywords: | Lacidipine L-type calcium current sodium current ventricular myocytes nimodipine nisoldipine patch-clamp |
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