Rises in intracellular Ca2+ induced by activation of glutamate receptors are of 
ultimate importance for neuronal excitability and pathophysiological processes. 
In the present study, we aimed to elucidate the types of voltage-dependent Ca2+ 
channels involved in the NMDA-stimulated influx of Ca2+ into the isolated rat 
retina by using selective blockers. Additionally, the number of binding sites 
for radioligands labelling L- ([3H]nitrendipine), N- ([125I]omega-conotoxin 
MVIIA) and P/Q-type ([125I]omega-conotoxin MVIIC) Ca2+ channels was assessed in 
the rat retina and, for further comparison, in the rat cortex. Incubation of 
isolated rat retinas with 100 microM NMDA produced a three-fold increase in the 
influx of 45Ca2+ that was completely blunted by MK-801, a NMDA receptor 
antagonist, and partially attenuated (approximately 20%) by tetrodotoxin, a Na+ 
channel blocker. The L-type Ca2+ channel blocker nifedipine reduced 
NMDA-stimulated Ca2+ influx in a dose-related fashion, with a maximum reduction 
of approximately 50%. Similar effects were observed with verapamil and 
diltiazem. Blockers of N- and P/Q-type Ca2+ channels had no significant effect 
on the influx of Ca2+ evoked by NMDA. Co2+, a non-specific Ca2+ channel blocker, 
caused an inhibition of NMDA-stimulated Ca2+ influx similar to that of 
nifedipine. Therefore, of all voltage-dependent Ca2+ channels, L-type channels 
appear to make the greatest contribution (up to 50%) to the NMDA-stimulated 
influx of Ca2+ into the isolated rat retina. This finding contrasts with 
evidence obtained in brain neurones supporting a role for L-, N- and P/Q-type 
channels in NMDA-evoked Ca2+ signals. A comparison of the number of radioligand 
binding sites associated with L-, N- or P/Q-type Ca2+ channels in the rat cortex 
and retina revealed that such a difference cannot be ascribed to a distinct 
expression pattern of these channels in both tissues, although some variations 
were found. Interestingly, a different affinity of [3H]nitrendipine for L-type 
Ca2+ channels in the rat retina and cortex was observed which may reflect the 
expression of different classes of L-type channels in these tissues. The ability 
of L-type Ca2+ channel blockers to attenuate NMDA-stimulated Ca2+ influx may 
underlie their neuroprotective effects in the retina.