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.