Abstract
Voltage-activated calcium currents (ICa) are one way by which calcium influx into neurons is mediated. To investigate changes in kinetic properties of ICa during neuronal development and to correlate possible kinetic changes with specific differentiation processes, the ICa of retinal ganglion cells (RGCs) was recorded with the perforated patch-clamp technique in rat retinal slices and in whole mounts at different prenatal and postnatal stages. ICa density increased between embryonic day (E) 20 and the adult stage, paralleled by a shift in activation of the omega-conotoxin GVIA-sensitive ICa toward more negative membrane potentials. Furthermore, developmental alterations were observed in ICa inactivation rate during a 120 msec test pulse and in steady-state inactivation of ICa. The most striking feature in ICa kinetics was a transient slowing of calcium current deactivation, which peaked at postnatal day (P)3-5 and affected all ICa subtypes. Although the shift in activation and the decreased inactivation rate of ICa can be explained by differential regulation of distinct calcium channel subtypes, it is more likely that a more general alteration of the cells' functional state was the underlying factor in alterations in steady-state inactivation and current deactivation of ICa. Alterations in the omega-conotoxin GVIA-sensitive and the toxin-resistant currents temporarily coincide with dendritic differentiation, and it is tempting to speculate about their role in network formation in the inner retina. In contrast, alterations in steady-state inactivation and current deactivation may be involved in the regulation of RGC survival, because they occur during the period of programmed cell death in the ganglion cell layer. In conclusion, distinct time windows of alterations in calcium channel properties were found, and this study has provided a basis for performing functional assays to clarify in detail the developmental process to which these alterations are related.