PHARMACOLOGICAL IDENTIFICATION OF A NOVEL CA(2+) CHANNEL IN CHICKEN BRAIN SYNAPTOSOMES

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Authors
  1. Lundy, P.M.
  2. Hamilton, M.G.
  3. Frew, R.
Corporate Authors
Defence Research Establishment Suffield, Ralston ALTA (CAN)
Abstract
Ca2+ influx was measured in rat and chicken brain synaptosomes in the presence of a number of pharmacological tools which have recently been used to define voltage-sensitive Ca2+-channel (VSCC) types. In chicken brain synaptosomes, VSCCs which, because of their sensitivity to inhibition by omega-conotoxin (omega-CgTx), are thought to be exclusively N-type, the P-type VSCC polyamine inhibitor FTX (from Agelenopsis aperta venom; 1 mu l/ml), its synthetic analogue, sFTX (1-5 mM) and the polypeptides AgalVA (IC50 0.29 muM) and omega-CgTx MVIIC (IC50 0.0022 muM) inhibited 70-100% of the measurable K+ stimulated CA2+ influx. The prototypical N-channel VSCC inhibitor omega-CgTx GVIA (IC50 0.014 muM), Cd2+ (50 muM) and diluted venom from Hololena curta (1:2,500) also caused complete or almost complete, inhibition of CA2+ influx. In comparable studies using rat brain synaptosomes, sFTX (1-10 mM) caused a dose-dependent reduction of CA2+ influx, while FTX (1 mu l/ml) and AgalVA (IC50 0.02 muM) completely inhibited CA2+ influx. Similar to the findings in chicken synaptosomes, Cd2+ (50 muM) and H.curta (1:2,500 dilution) both inhibited K+ stimulated influx by >80% whereas omega-CgTx(1 muM) only caused a maximum 25% inhibition. Both sFTX and its congener spermine, inhibited (125I)omega-CgTx binding to rat and chicken synaptosomal memberanes. These results strongly implicate P-type channels as the major VSCC in rat brain. TRUNCATED
Keywords
Calcium channel inhibitors;Neurotransmitter;Agatoxin-IVA
Date of publication
28 Dec 1993
Number of Pages
7
Reprinted from
Brain Research, no 643, 1994, p 204-210
DSTKIM No
97-00778
CANDIS No
144046
Format(s):
Hardcopy;Document Image stored on Optical Disk

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