Isradipine

L-type (Ca_V1), 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 and therefore were recognized as a therapeutic target for cardiovascular diseases^1,2.

Isradipine is a dihydropyridine that acts as a L-type, voltage-gated Ca²⁺ channel blocker and is used in the clinic to treat hypertension^3,4. Isradipine inhibits L-type channels expressed in Xenopus oocytes with IC₅₀ = 0.2 µM at a holding potential of -80 mV and the inhibition is state dependent and increases with reduced membrane hyperpolarization⁴. Slow excitatory synaptic currents in dopaminergic neurons in slices of rat substantia nigra pars compacta and ventral tegmental area, which were evoked by a train of focally delivered electrical stimuli, were depressed by isradipine (30 nM-100 µM) in a concentration-dependent and reversible manner⁵. In addition, isradipine, was shown recently to be a putative effective treatment for Parkinson’s disease, by affecting particularly the excitability of certain Ca_V1.3 expressing dopaminergic neurons⁶. In a pancreatic cell line, insulin secretion triggered by 16.7 mM glucose, was completely abolished by 5 µM isradipine⁷.