Voltage-dependent calcium channels in the rat retina: Involvement in NMDA-stimulated influx of calcium

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- ([H-3]nitrendipine). N- [I-125]omega -conotoxin MVIIA and P/Q-type ([I-125]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 mu< NMDA produced a three-fold increase in the influx of Ca-45(2+) that was completely blunted by MK-801, a NMDA receptor antagonist, and partially attenuated (approximately 20%) by tetrodutoxin, 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 NR IDA. 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-stimulate 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 [H-3]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. <(c)> 2001 Academic Press.