title: Nimodipine inhibits AP firing in cultured hippocampal neurons predominantly due to block of voltage-dependent potassium channels.
abstract: L-type calcium channels (LTCC) are important functional elements of hippocampal neurons contributing to processes like memory formation and gene expression. Mice lacking the Ca(V)1.2 channel in hippocampal pyramidal cells exhibited defects in spatial memory (Moosmang et al. 2005) and lowered frequency of repetitive action potential (AP) firing (Lacinova et al. 2008). We tested the contribution of LTCC to AP firing of cultured rat neonatal hippocampal neurons using the dihydropyridine channel blocker nimodipine. Ionic currents and APs were recorded in the whole cell patch clamp configuration. A prolonged depolarizing current pulse activated the firing of a series of APs. The presence of 10 μM nimodipine blocked all but the first AP in series. This concentration, which is potent enough to completely block LTCC, inhibited about 35-50% of the total calcium current. In addition, nimodipine blocked about 50% of both calcium-dependent and voltage-dependent potassium currents whereas the sodium current was not affected. We suggest that nimodipine suppressed the firing of APs in cultured neonatal rat hippocampal neurons due to inhibition of both calcium and potassium currents.
authors.affiliation: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Anton
authors.initials: A
authors.lastname: Caro
authors.forename: Bohumila
authors.initials: B
authors.lastname: Tarabova
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rojo-Ruiz
authors.forename: Lubica
authors.initials: L
authors.lastname: Lacinova
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*; D051381:Rats; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D001464:Barium; D009553:Nimodipine; D011188:Potassium; D002118:Calcium