Effects of Ca2+ channel blockers on directional selectivity of rabbit retinal ganglion cells

1. Extracellular recordings were made from ON-OFF directionally selective ganglion cells in superfused rabbit retinas in order to examine the effects of voltage-activated Ca2+ channel blockers on the response of these ganglion cells to a moving bar of light. 2. Bath application of Cd2+ (67-110 microM) abolished directional selectivity in the ganglion cells. That is, the cells gave nearly equal responses to the leading and trailing edges of a bar of light moved in the preferred and null directions. This effect of Cd2+ was rapidly reversible. 3. Directional selectivity in the ganglion cells was not affected by Ni2+ (120-440 microM), Co2+ (180-690 microM), or the L-type Ca2+ channel blockers nicardipine (7-29 microM) and methoxyverapamil (18-60 microM). These blockers did, however, reduce the responses of the ganglion cells to a bar of light moved in the preferred direction. 4. omega-Conotoxin MVIIC (130 nM-1.9 microM), which potently blocks N-type and Q-type Ca2+ channels, abolished directional selectivity in the ganglion cells. omega-Conotoxin MVIIC not only brought out large leading and trailing edge responses to movement of a bar of light in the null direction, but it also increased the leading and trailing edge responses to movement of the bar of light in the preferred direction. The effect of omega-conotoxin MVIIC was slowly reversible. 5. The N-type Ca2+ channel blocker omega-conotoxin GVIA (1.4-6.3 microM) did not abolish directional selectivity in the ganglion cells. This blocker did, however, bring out some response to the leading edge of a bar of a light moved in the null direction. This effect of omega-conotoxin GVIA appeared to be irreversible. 6. omega-Agatoxin IVA, a potent blocker of P-type Ca2+ channels, when bath applied at low concentrations (66-83 nM), increased the responses to movement of a bar of light in the preferred direction but brought out only small responses to movement of the bar of light in the null direction. At high concentrations (250-280 nM) that reportedly block Q-type Ca2+ channels by > or = 50%, omega-agatoxin IVA nearly abolished directional selectivity. This effect of omega-agatoxin IVA was slowly reversible. 7. These results indicate that omega-conotoxin MVIIC- and omega-agatoxin IVA-sensitive Ca2+ channels (possibly Q-type channels) play an important role in the generation of directional selectivity in rabbit retinal ganglion cells.