title: Calcium channels involved in K+- and veratridine-induced increase of cytosolic calcium concentration in human cerebral cortical synaptosomes.
abstract: Human cerebral cortical synaptosomes were used to study voltage-dependent Ca(2+) channels mediating calcium influx in human axon terminals. Synaptosomes were depolarized by elevation of the extracellular K(+) concentration by 30 mM or by the addition of veratridine (10 microM). Increase in cytosolic concentration of calcium [Ca(2+)](i) induced by either stimulus was abolished in the absence of extracellular Ca(2+) ions. omega-Agatoxin IVA inhibited the K(+)-induced [Ca(2+)](i) increase concentration-dependently (IC(50): 113 nM). omega-Conotoxin GVIA (0.1 microM) inhibited K(+)-induced [Ca(2+)](i) increase by 20%. omega-Conotoxin MVIIC (0.2 microM) caused an inhibition by 85%. Nifedipine (1 microM) had no effect on K(+)-induced [Ca(2+)](i) increase. Veratridine-induced increase in [Ca(2+)](i) was inhibited by omega-conotoxin GVIA (0.1 microM) and omega-Agatoxin IVA (0.2 microM; by about 25 and 45%, respectively). Nifedipine inhibited the veratridine-evoked [Ca(2+)](i) increase concentration-dependently (IC(50): 4.9 nM); Bay K 8644 (3 microM) shifted the nifedipine concentration-response curve to the right. Mibefradil (10 microM) abolished the increase in [Ca(2+)](i) evoked by K(+) and reduced the increase evoked by veratridine by almost 90%. KB-R7943 (3 microM) an inhibitor of the Na(+)/Ca(2+) exchanger NCX1, decreased the increase in [Ca(2+)](i) evoked by veratridine by approximately 20%. It is concluded that the increase in [Ca(2+)](i) after K(+) depolarization caused by Ca(2+) influx predominantly via P/Q-type Ca(2+) channels and after veratridine depolarization via N- and P/Q-type, but also by L-type Ca(2+) channels. The toxin- and nifedipine-resistant fraction of the veratridine response may result both from influx via R-type Ca(2+) channels and by Ca(2+) inward transport via Na(+)/Ca(2+) exchanger.
authors.affiliation: Department of Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Meder
authors.forename: K
authors.initials: K
authors.lastname: Fink
authors.forename: J
authors.initials: J
authors.lastname: Zentner
authors.forename: M
authors.initials: M
authors.lastname: Göthert
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D002648:Child; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014701:Veratridine; D013890:Thiourea; D011188:Potassium; D002118:Calcium