Pharmacological characterisation of the calcium channels coupled to the plateau phase of KCl-induced intracellular free Ca2+ elevation in chicken and rat synaptosomes.
The effect of various blockers of voltage operated calcium channels (VOCCs) was studied on the non-inactivating, plateau phase of KCl-induced intracellular free Ca2+ ([Ca2+]i) elevation in rat cortical and chicken forebrain synaptosomes. In chicken synaptosomes, omega-CgTx GVIA (0.1 nM to 1 microM) and omega-CgTx MVIIA (0.1 nM to 1 microM), both selective blockers of N-type Ca2+ channels, produced a concentration-dependent inhibition of the plateau phase of [Ca2+]i elevation. omega-CgTx GVIA (IC50 value 28 nM) was more potent than omega-CgTx MVIIA (IC50 value 78 nM), but at submaximal concentrations, took longer to reach its maximum effect (20 min for omega-CgTx GVIA; 10 min for omega-CgTx MVIIA). At 1 microM, the highest concentration tested, each toxin blocked > 85% of [Ca2+]i elevation. The effect of omega-CgTx GVIA on the extent and time-course of inhibition of [Ca2+]i elevation was maintained in a Na(+)-free, choline substituted, medium. omega-Aga IVA (300 nM), a selective blocker of P-type calcium channels, inhibited 28 +/- 5% of [Ca2+]i elevation. The effect of a combination of submaximal inhibitory concentrations of omega-CgTx GVIA (100 nM) and omega-Aga IVA (300 nM) was less than additive. In rat synaptosomes, omega-CgTx GVIA (1 microM) and omega-CgTx MVIIA (1 microM), blocked only 18 +/- 5% and 17 +/- 4% of the plateau phase of free Ca2+ elevation, respectively. omega-Aga IVA produced a concentration-dependent inhibition of [Ca2+]i elevation in this preparation. Threshold inhibition was observed at 1 nM, and maximum inhibition (64 +/- 8%) at 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
Bowman
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Lilly Research Centre, Windlesham, Surrey, U.K.
Alexander
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Lodge
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002645:Chickens; D066298:In Vitro Techniques; D011189:Potassium Chloride / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011189:Potassium Chloride; D002118:Calcium