Choi, Kee-Hyun Rhim, Hyewhon 2024-01-20T20:01:56Z 2024-01-20T20:01:56Z 2021-09-02 2010-01-25 0014-2999 https://pubs.kist.re.kr/handle/201004/131773 Low voltage-activated T-type calcium channels are involved in the regulation of the neuronal excitability, and could be subject to many antipsychotic drugs. The effects of clozapine, an atypical antipsychotic drug, on recombinant Ca(v)3.1 T-type calcium channels heterologously expressed in human embryonic kidney 293 cells were examined using whole-cell patch-clamp recordings. At a standard holding potential of -100mV, clozapine inhibited Ca(v)3.1 currents with an IC50 value of 23.7 +/- 1.3 mu M in a use-dependent manner. However, 10 mu M clozapine inhibited more than 50% of the Ca(v)3.1 currents in recordings at a more physiologically relevant holding potential of -75 mV. Clozapine caused a significant hyperpolarizing shift in the steady-state inactivation curve of the Ca(v)3.1 channels, which is presumably the main mechanism accounting for the inhibition of the Ca(v)3.1 currents. In addition, clozapine slowed Ca(v)3.1 deactivation and inactivation kinetics but not activation kinetics. Clozapine-induced changes in deactivation and inactivation rates of the Ca(v)3.1 channel gating would likely facilitate calcium influx via Ca(v)3.1 T-type calcium channels. Thus, clozapine may exert its therapeutic and/or side effects by altering cell's excitability and firing proper-ties through actions on T-type calcium channels. (C) 2009 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV CA2+ CHANNELS PHARMACOLOGICAL-PROPERTIES ABSENCE SEIZURES SENSORY NEURONS XENOPUS OOCYTES RAT CELLS RECEPTORS NEUROLEPTICS MIBEFRADIL Inhibition of recombinant Ca(v)3.1 (alpha(1G)) T-type calcium channels by the antipsychotic drug clozapine Article 10.1016/j.ejphar.2009.09.035 1 EUROPEAN JOURNAL OF PHARMACOLOGY, v.626, no.2-3, pp.123 - 130 EUROPEAN JOURNAL OF PHARMACOLOGY 626 2-3 123 130 scie scopus 000274090800002 2-s2.0-70649101232 Pharmacology & Pharmacy Pharmacology & Pharmacy Article CA2+ CHANNELS PHARMACOLOGICAL-PROPERTIES ABSENCE SEIZURES SENSORY NEURONS XENOPUS OOCYTES RAT CELLS RECEPTORS NEUROLEPTICS MIBEFRADIL T-type calcium channel Ca(v)3.1 alpha(1G) subunit Clozapine Antipsychotics Neuroleptics