TY - JOUR T1 - Calcium Channels Involved in K<sup>+</sup>- and Veratridine-Induced Increase of Cytosolic Calcium Concentration in Human Cerebral Cortical Synaptosomes JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1126 LP - 1131 VL - 290 IS - 3 AU - Wolfgang Meder AU - Klaus Fink AU - Josef Zentner AU - Manfred Göthert Y1 - 1999/09/01 UR - http://jpet.aspetjournals.org/content/290/3/1126.abstract N2 - Human cerebral cortical synaptosomes were used to study voltage-dependent Ca2+ 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 μM). Increase in cytosolic concentration of calcium [Ca2+]i induced by either stimulus was abolished in the absence of extracellular Ca2+ions. ω-Agatoxin IVA inhibited the K+-induced [Ca2+]i increase concentration-dependently (IC50: 113 nM). ω-Conotoxin GVIA (0.1 μM) inhibited K+-induced [Ca2+]iincrease by 20%. ω-Conotoxin MVIIC (0.2 μM) caused an inhibition by 85%. Nifedipine (1 μM) had no effect on K+-induced [Ca2+]i increase. Veratridine-induced increase in [Ca2+]i was inhibited by ω-conotoxin GVIA (0.1 μM) and ω-Agatoxin IVA (0.2 μM; by about 25 and 45%, respectively). Nifedipine inhibited the veratridine-evoked [Ca2+]i increase concentration-dependently (IC50: 4.9 nM); Bay K 8644 (3 μM) shifted the nifedipine concentration-response curve to the right. Mibefradil (10 μM) abolished the increase in [Ca2+]i evoked by K+ and reduced the increase evoked by veratridine by almost 90%. KB-R7943 (3 μM) an inhibitor of the Na+/Ca2+ exchanger NCX1, decreased the increase in [Ca2+]i evoked by veratridine by approximately 20%. It is concluded that the increase in [Ca2+]i after K+ depolarization caused by Ca2+ influx predominantly via P/Q-type Ca2+ channels and after veratridine depolarization via N- and P/Q-type, but also by L-type Ca2+ channels. The toxin- and nifedipine-resistant fraction of the veratridine response may result both from influx via R-type Ca2+ channels and by Ca2+ inward transport via Na+/Ca2+exchanger. The American Society for Pharmacology and Experimental Therapeutics ER -