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Related Experiment Video

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Whole-Cell Recording of Calcium Release-Activated Calcium CRAC Currents in Human T Lymphocytes
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Lercanidipine and T-type calcium current.

E Cerbai1, A Mugelli

  • 1Department of Neurosciences, Psychology, Drug Research and Child's Health (NEUROFARBA), University of Florence, Florence, Italy. alessandro.mugelli@unifi.it.

European Review for Medical and Pharmacological Sciences
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Summary
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Lercanidipine, a calcium channel blocker, exhibits selectivity for T-type over L-type calcium channels. This study reveals lercanidipine

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Area of Science:

  • Pharmacology
  • Cardiovascular Research

Background:

  • Lercanidipine is a calcium antagonist known for its antihypertensive and reno-protective effects.
  • Previous studies confirmed lercanidipine's blockade of L-type calcium channels (CaL).
  • Data on lercanidipine's effects on T-type calcium channels (CaT) were previously unavailable.

Purpose of the Study:

  • To evaluate the effects of R-lercanidipine, S-lercanidipine, and RS-lercanidipine on both CaL and CaT.
  • To determine the selectivity ratio of lercanidipine enantiomers and racemate for CaT versus CaL.
  • To compare lercanidipine's channel selectivity with other dihydropyridines and a known CaT blocker.

Main Methods:

  • Patch-clamp electrophysiology on guinea-pig ventricular myocytes.
  • Application of a voltage protocol mimicking cardiac action potentials.
  • Superfusion with a modified extracellular solution to isolate calcium currents.

Main Results:

  • Lercanidipine, in its racemic and enantiomeric forms, demonstrated notable T-type calcium channel selectivity.
  • The T/L selectivity ratio for lercanidipine ranged from 1.05 to 1.15.
  • Compared to other dihydropyridines like amlodipine and lacidipine, lercanidipine exhibited higher T/L selectivity.

Conclusions:

  • All tested calcium channel blockers possess both T- and L-channel blocking activities.
  • Lercanidipine displays the highest T/L selectivity among the evaluated dihydropyridines.
  • The differential affinity for T- and L-type calcium channels distinguishes various calcium channel blockers.