Nicergoline inhibits T‐type Ca2+ channels in rat isolated hippocampal CA1 pyramidal neurones

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Abstract
1 The effects of nicergoline on the T- and L-type Ca2+ currents in pyramidal cells freshly isolated from rat hippocampal CA1 region were investigated by use of a ‘concentration-clamp’ technique. The technique combines a suction-pipette technique, which allows intracellular perfusion under a single-electrode voltage-clamp, and rapid exchange of extracellular solution within 2 ms. 2 T-type Ca2+ currents were evoked by step depolarizations from a holding potential of −100 mV to potentials more positive than −70 to −60 mV, and reached a peak at about −30 mV in the current-voltage relationship. Activation and inactivation of T-type Ca2+ currents were highly potential-dependent. 3 Nicergoline and other Ca2+ antagonists dose-dependently blocked the T-type Ca2+ channel with an order of potency nicardipine > nicergoline > diltiazem. 4 The L-type Ca2+ channel was also blocked in the order nicardipine > nicergoline > diltiazem, although the T-type Ca2+ channel was more sensitive to nicergoline. 5 The inhibitory effects of nicergoline and nicardipine on the T-type Ca2+ current were voltage-, time-, and use-dependent, and the inhibition increased with a decrease in the external Ca2+ concentration. Diltiazem showed only a use-dependent block.