Overview
- Burges, R.A. et al. (1987) J. Cardiovasc. Pharmacol. 9, 110.
- Julius, S. et al. (2004) Lancet 363, 2022.
- Furukawa, T. et al. (2005) J. Cardiovasc. Pharmacol. 45, 241.
Alomone Labs Amlodipine inhibits L-type voltage-gated Ca2+ currents heterologously expressed in Xenopus oocytes.A. Time course of CaV1.2/α2-δ1/β2a (L-type) current inhibition by 10 µM Amlodipine (#A-110). Currents were elicited by application of voltage steps from a holding potential of -100 mV to 0 mV (100 msec). B. Superimposed example traces of current responses before and during perfusion of 10 µM Amlodipine as indicated.
L-type (CaV1) voltage-gated Ca2+ channels are plasma membrane protein complexes which allow the passage of Ca2+ ions into cells following depolarization of the membrane potential. L-type channels are widely expressed in cardiac and smooth muscle where they control contraction. Consequently, these channels were recognized as a therapeutic target for cardiovascular diseases1,2.
Dihydropyridines (DHP) are molecules that act as allosteric modulators of L-type channels. Many are used in the clinic to treat hypertension2,3. Amlodipine besylate is a DHP that acts as an L-type, voltage-gated Ca2+ channel blocker and is used in the clinic to treat hypertension3,4. Amlodipine inhibits Ca2+-induced contractions in depolarised rat aorta (IC50 1.9 nM) but displays a very slow action onset. Contractions induced by depolarising steps with 45 mM K+ are far less potently blocked by amlodipine (IC50 19.4 nM) and guinea pig papillary muscle single-cell slow action potentials are blocked at a concentration of 5 mM4. Amlodipine besylate inhibits L- and T-type CaV channels with similar potency5.
