title: L-type Ca2+ channel antagonists block voltage-dependent Ca2+ channels in identified leech neurons.
abstract: We investigated the effect of L-type Ca2+ channel antagonists on the Ca2+ influx through voltage-gated Ca2+ channels in leech Retzius, Leydig, AP, AE, P, and N neurons. The efficacy of the antagonists was quantified by monitoring their effect on the increase in the intracellular free Ca2+ concentration ([Ca2+]i; measured by Fura-2) that was induced by depolarizing the cell membrane by raising the extracellular K+ concentration. This K+-induced [Ca2+]i increase was blocked by the phenylalkylamines verapamil, gallopamil, and devapamil, the benzothiazepine diltiazem, as well as by the 1,4-dihydropyridine nifedipine. The blocking effect of the three phenylalkylamines was similar, being most pronounced in P and N neurons and smaller in Leydig, Retzius, AP, and AE neurons. Contrastingly, diltiazem and nifedipine were similarly effective in the neurons investigated, whereby their efficacy was like that of the phenylalkylamines in Retzius, Leydig, AP, and AE neurons. Depending on cell type and blocking agent, the concentrations necessary to suppress the K+-induced [Ca2+]i increase by 50% were estimated to vary between 5 and 190 microM. At high concentrations, the phenylalkylamines and diltiazem by themselves caused a marked [Ca2+]i increase in Leydig, P, and N neurons, which is probably due to activation of the caffeine-sensitive ion channels present in the plasma membrane of these cells. Together with previous observations, the results indicate a distant relationship of the voltage-gated Ca2+ channels present in many if not all leech neurons to vertebrate L-type Ca2+ channels.
authors.affiliation: Institut für Neurobiologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany. dierkes@uni-duesseldorf.de
authors.forename: Paul Wilhelm
authors.initials: PW
authors.lastname: Dierkes
authors.forename: Verena
authors.initials: V
authors.lastname: Wende
authors.forename: Peter
authors.initials: P
authors.lastname: Hochstrate
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schlue
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D007865:Leeches / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014700:Verapamil / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010726:Phosphodiesterase Inhibitors; D005711:Gallopamil; D002110:Caffeine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; C055885:devapamil