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

摘要

The spontaneous discharge patterns of developing retinal ganglion cells are thought to play a crucial role in the refinement of early retinofugal projections. To investigate the contributions of intrinsic membrane properties to the spontaneous activity of developing ganglion cells, we assessed the effects of blocking large and small calcium-activated potassium conductances on the temporal pattern of such discharges by means of patch-clamp recordings from the intact retina of developing ferrets. Application of apamin and charybdotoxin (CTX), which selectively block the small and large calcium-activated potassium channels, respectively, resulted in significant changes in spontaneous firings. In cells recorded from the oldest animals [postnatal day 30 (P30)-P45], which manifested relatively sustained discharge patterns, application of either blocker induced bursting activity. With CTX the bursts were highly periodic, short in duration, and of high frequency. In contrast, 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 analysis of discharge patterns. Filling cells from which recordings were made with Lucifer yellow revealed that these effects were obtained in all three morphological classes of cells: alpha, beta, and gamma. These findings provide the first evidence that apamin- and CTX-sensitive K+ conductances can have differential effects on the spontaneous discharge patterns of retinal ganglion cells. Remarkably, the bursts of activity obtained after apamin application in more mature neurons appeared very similar to the spontaneous bursting patterns observed in developing neurons. These findings suggest that the maturation of calcium-activated potassium channels, particularly the apamin-sensitive conductance, may contribute to the changes in spontaneous firings exhibited by retinal ganglion cells during the course of normal development.