Differential effects of apamin- and charybdotoxin-sensitive K+ conductances on spontaneous discharge patterns of developing retinal ganglion cells

The spontaneous discharge patterns of developing retinal ganglion cells are thought to play a crucial role in the refinement of early retinofugal proj ections. To investigate the contributions of intrinsic membrane properties to the spontaneous activity of developing ganglion cells, we assessed the e ffects of blocking large and small calcium-activated potassium conductances on the temporal pattern of such discharges by means of patch-clamp recordi ngs from the intact retina of developing ferrets. Application of apamin and charybdotoxin (CTX), which selectively block the small and large calcium-a ctivated potassium channels, respectively, resulted in significant changes in spontaneous firings. In cells recorded from the oldest animals [postnata l day 30 (P30)-P45], which manifested relatively sustained discharge patter ns, application of either blocker induced bursting activity. With CTX the b ursts were highly periodic, short in duration, and of high frequency. In co ntrast, with apamin the interburst intervals were longer, less regular, and lower in overall spike frequency. These differences between the effects of the two blockers on spontaneous activity were documented by spectral analy sis of discharge patterns. Filling cells from which recordings were made wi th Lucifer yellow revealed that these effects were obtained in all three mo rphological classes of cells: alpha, beta, and gamma. These findings provid e the first evidence that apamin- and CTX-sensitive K+ conductances can hav e differential effects on the spontaneous discharge patterns of retinal gan glion cells. Remarkably, the bursts of activity obtained after apamin appli cation in more mature neurons appeared very similar to the spontaneous burs ting patterns observed in developing neurons. These findings suggest that t he maturation of calcium-activated potassium channels, particularly the apa min-sensitive conductance, may contribute to the changes in spontaneous fir ings exhibited by retinal ganglion cells during the course of normal develo pment.