Calcium channels involved in K+- and veratridine-induced increase of cytosolic calcium concentration in human cerebral cortical synaptosomes.

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.

[1]  K. Fink,et al.  Involvement of different calcium channels in K+- and veratridine-induced increases of cytosolic calcium concentration in rat cerebral cortical synaptosomes , 1997, Naunyn-Schmiedeberg's Archives of Pharmacology.

[2]  M. Staufenbiel,et al.  574 Localization and functional significance of presenilin S182 , 1996, Neurobiology of Aging.

[3]  H. Reuter,et al.  A Role of Intracellular Na+ in the Regulation of Synaptic Transmission and Turnover of the Vesicular Pool in Cultured Hippocampal Cells , 1996, Neuron.

[4]  J. Kimura,et al.  A novel antagonist, No. 7943, of the Na+/Ca2+ exchange current in guinea‐pig cardiac ventricular cells , 1996, British journal of pharmacology.

[5]  T. Iwamoto,et al.  A Novel Isothiourea Derivative Selectively Inhibits the Reverse Mode of Na+/Ca2+ Exchange in Cells Expressing NCX1* , 1996, The Journal of Biological Chemistry.

[6]  G. Fontana,et al.  The Na+‐Ca2+ Exchanger in Rat Brain Synaptosomes , 1996, Annals of the New York Academy of Sciences.

[7]  M. Blaustein,et al.  Localization of the Na+‐Ca2+ Exchanger in Vascular Smooth Muscle, and in Neurons and Astrocytesa , 1996, Annals of the New York Academy of Sciences.

[8]  J. Gilmore,et al.  The effects of ifenprodil and eliprodil on voltage-dependent Ca2+ channels and in gerbil global cerebral ischaemia. , 1996, European journal of pharmacology.

[9]  H. Reuter,et al.  Localization and functional significance of the Na+/Ca2+exchanger in presynaptic boutons of hippocampal cells in culture , 1995, Neuron.

[10]  R. Tsien,et al.  Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967). , 1995, Molecular pharmacology.

[11]  E. J. Fletcher,et al.  Blockade by ifenprodil of high voltage‐activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones: comparison with N‐methyl‐D‐aspartate receptor antagonist actions , 1994, British journal of pharmacology.

[12]  S. Mishra,et al.  Selective inhibition of T-type Ca2+ channels by Ro 40-5967. , 1994, Circulation research.

[13]  B. Scatton,et al.  The NMDA receptor antagonist eliprodil (SL 82.0715) blocks voltage-operated Ca2+ channels in rat cultured cortical neurons. , 1994, European journal of pharmacology.

[14]  J. Luebke,et al.  Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus , 1993, Neuron.

[15]  M. Adams,et al.  Analysis of rapid calcium signals in synaptosomes , 1993, Neurochemistry International.

[16]  G. Fontana,et al.  Calcium Buffering and Free Ca2+ in Rat Brain Synaptosomes , 1993, Journal of neurochemistry.

[17]  B. Bean,et al.  A new conus peptide ligand for mammalian presynaptic Ca2+ channels , 1992, Neuron.

[18]  H. Breer,et al.  Rapid kinetics of depolarization-induced changes in intrasynaptosomal calcium concentrations , 1992, Neurochemistry International.

[19]  M. Adams,et al.  P-type calcium channels blocked by the spider toxin ω-Aga-IVA , 1992, Nature.

[20]  C. Duarte,et al.  Synaptosomal [Ca2+]i as influenced by Na+/Ca2+ exchange and K+ depolarization. , 1991, Cell calcium.

[21]  R. Mulkey,et al.  Action potentials must admit calcium to evoke transmitter release , 1991, Nature.

[22]  D. Nicholls,et al.  Repetitive Action Potentials in Isolated Nerve Terminals in the Presence of 4‐Aminopyridine: Effects on Cytosolic Free Ca2+ and Glutamate Release , 1989, Journal of neurochemistry.

[23]  K. Mine,et al.  Is the Augmentation of K+‐Evoked Intrasynaptosomal Ca2+ Concentration Due to the Influx of Ca2+ in Rat Brain Synaptosomes? , 1989, Journal of neurochemistry.

[24]  M. Murawsky,et al.  Further Characterization of Phasic Calcium Influx in Rat Cerebrocortical Synaptosomes: Inferences Regarding Calcium Channel Type(s) in Nerve Endings , 1989, Journal of neurochemistry.

[25]  T. Godfraind,et al.  The actions of nifedipine and nisoldipine on the contractile activity of human coronary arteries and human cardiac tissue in vitro. , 1987, Pharmacology & toxicology.

[26]  E. Ogata,et al.  BAY-K-8644, a calcium channel agonist, induces a rise in cytoplasmic free calcium and iodide discharge in thyroid cells. , 1987, Biochemical and biophysical research communications.

[27]  E. Ligeti,et al.  Calcium uptake of rat brain synaptosomes as a function of membrane potential under different depolarizing conditions. , 1986, The Journal of physiology.

[28]  M. Bechem,et al.  The optical isomers of the 1,4-dihydropyridine BAY K 8644 show opposite effects on Ca channels. , 1985, European journal of pharmacology.

[29]  R. Tsien,et al.  Three types of neuronal calcium channel with different calcium agonist sensitivity , 1985, Nature.

[30]  D. Nachshen.  Regulation of cytosolic calcium concentration in presynaptic nerve endings isolated from rat brain. , 1985, The Journal of physiology.

[31]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[32]  D. Yoshikami,et al.  A venom peptide with a novel presynaptic blocking action , 1984, Nature.

[33]  M. Blaustein,et al.  Membrane potentials in pinched‐off presynaptic nerve ternimals monitored with a fluorescent probe: evidence that synaptosomes have potassium diffusion potentials. , 1975, The Journal of physiology.

[34]  M. Blaustein.  Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro. , 1975, The Journal of physiology.

[35]  Y. Mori,et al.  Molecular pharmacology of voltage-dependent calcium channels. , 1996, Japanese journal of pharmacology.