GADOLINIUM AND NEOMYCIN BLOCK VOLTAGE-SENSITIVE CA2-CA2+ ANTIPORTER IN BRAIN NERVE-ENDINGS( CHANNELS WITHOUT INTERFERING WITH THE NA+)

The rare earth lanthanide gadolinium (Gd3+), in concentrations ranging from 1 to 100 muM, reduced the elevation of intracellular Ca2+ concen tration [Ca2+]i, monitored by means of the fluorescent probe fura-2. I t also decreased the influx of Ca-45(2+) through voltage sensitive cal cium channels (VSCC), induced by 55 mM K+ in Percoll-purified brain sy naptosomes. By contrast, Gd3+ (0.1-30 muM) did not interfere with Na+- dependent Ca-45(2+) uptake, a process which expresses Na+-Ca2+ exchang e activity. The aminoglycoside neomycin displayed a similar pattern of activity although at higher concentrations (300-1000 muM). At the sam e range of concentrations (100 and 300 muM), the phenylalkylamine, ver apamil, blocked both Ca2+ entry through VSCC and Ca2+ influx through t he Na+-Ca2+ exchanger. Finally, nimodipine failed to prevent Ca-45(2+) influx in either case, and fura-2 monitored [Ca2+]i elevation induced by high K+- or Na+-dependent Ca-45(2+) 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 interferenc e with the Na+-Ca2+ antiporter, whereas the inhibitory action of verap amil does not discriminate between Ca2+ entry through VSCC or the anti porter.