Gadolinium and neomycin block voltage-sensitive Ca2+ channels without interfering with the Na(+)-Ca2+ antiporter in brain nerve endings.
The rare earth lanthanide gadolinium (Gd3+), in concentrations ranging from 1 to 100 microM, reduced the elevation of intracellular Ca2+ concentration [Ca2+]i, monitored by means of the fluorescent probe fura-2. It also decreased the influx of 45Ca2+ through voltage sensitive calcium channels (VSCC), induced by 55 mM K+ in Percoll-purified brain synaptosomes. By contrast, Gd3+ (0.1-30 microM) did not interfere with Na(+)-dependent 45Ca2+ uptake, a process which expresses Na(+)-Ca2+ exchange activity. The aminoglycoside neomycin displayed a similar pattern of activity although at higher concentrations (300-1000 microM). At the same range of concentrations (100 and 300 microM), the phenylalkylamine, verapamil, blocked both Ca2+ entry through VSCC and Ca2+ influx through the Na(+)-Ca2+ exchanger. Finally, nimodipine failed to prevent 45Ca2+ influx in either case, and fura-2 monitored [Ca2+]i elevation induced by high K(+)- or Na(+)-dependent 45Ca2+ uptake. Collectively, the data obtained in the present study indicate that Gd3+ and neomycin can be considered to be valid pharmacological tools for selective blocking of VSCC in cerebral nerve terminals, without any concomitant interference with the Na(+)-Ca2+ antiporter, whereas the inhibitory action of verapamil does not discriminate between Ca2+ entry through VSCC or the antiporter.
Department of Human Communication Science, School of Medicine Federico II, University of Naples, Italy.
L M
LM
Canzoniero
M
M
Taglialatela
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G
Di Renzo
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L
Annunziato
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D016257:Fura-2; D005682:Gadolinium / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019831:Sodium-Calcium Exchanger; D009553:Nimodipine; D005682:Gadolinium; D014700:Verapamil; D009355:Neomycin; D011188:Potassium; D002118:Calcium; D016257:Fura-2