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Effects of dihydropyridine calcium antagonists on rat midbrain dopaminergic neurones
Author(s) -
Mercuri Nicola B.,
Bond Antonello,
Calabresi Paolo,
Stratta Francesca,
Stefani Alessandro,
Bernardi Giorgio
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17068.x
Subject(s) - dihydropyridine , nimodipine , nifedipine , chemistry , calcium , bay k8644 , voltage dependent calcium channel , calcium channel , bursting , afterdepolarization , pharmacology , endocrinology , medicine , electrophysiology , neuroscience , biology , organic chemistry , repolarization
1 The effects of the dihydropyridine calcium channel antagonists, nifedipine and nimodipine (300 n m ‐30 μ m ) were tested in vitro on intracellularly recorded dopaminergic neurones in the rat ventral mesencephalon. 2 Bath applied nifedipine and nimodipine inhibited in a concentration‐dependent manner the spontaneous firing discharge of the action potentials, whereas, the dihydropyridine calcium channel agonist, Bay K 8644 increased the firing rate. 3 Pacemaker oscillations and bursts of action potentials were produced by loading the cells with caesium. Nifedipine and nimodipine reduced the rate and the duration of the caesium‐induced membrane oscillations and decreased the number of action potentials in a burst. During the blockade of potassium currents the dopaminergic neurones often developed a prolonged (100–800 ms) afterdepolarization that was also inhibited by dihydropyridines. 4 The spontaneous discharge of calcium spikes was also inhibited by both dihydropyridine calcium antagonists. The apparent input resistance and the level of membrane potential were not affected by the dihydropyridine calcium antagonists. 5 If the action potential duration was less than 150 ms the shape of the spike was not clearly influenced by both calcium antagonists. However, when the duration of the action potential was longer than 150–200 ms due to the intracellular injection of caesium ions plus the extracellular application of tetraethylammonium (10–50 μ m ), both nifedipine and nimodipine reversibly shortened the plateau potential. 6 It is suggested that nifedipine and nimodipine depress the rhythmic and bursting activity of the dopaminergic cells and shorten the calcium action potential by blocking dihydropyridine‐sensitive high‐threshold calcium currents.