Nicergoline inhibits T-type Ca2+ channels in rat isolated hippocampal CA1 pyramidal neurones.
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 greater than nicergoline greater than diltiazem. 4. The L-type Ca2+ channel was also blocked in the order nicardipine greater than nicergoline greater than 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.
Takahashi
K
K
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
Akaike
N
N
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D009530:Nicergoline / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000166:cytology / Q000378:metabolism*; D051381:Rats
D015220:Calcium Channels; D009529:Nicardipine; D004110:Diltiazem; D009530:Nicergoline