Ion conductances related to development of repetitive firing in mouse retinal ganglion neurons in situ

In the retina, the ability to encode graded depolarizations into spike trai ns of variable frequency appears to be a specific property of retinal gangl ion neurons (RGNs). To deduce the developmental changes in ion conductances underlying the transition from single to repetitive firing, patch-clamp re cordings were performed in the isolated mouse retina between embryonic day 15 (E15) and postnatal day 5 (P5). Immature neurons of the E15 retina were selected according to their capacity to generate voltage-activated Na+ curr ents (I-Na(V)). Identification of P5 RGNs was based on retrograde labeling, visualization of the axon, or the amplitude of I-Na(V). At E15, half of th e cells were excitable but none of them generated more than one spike. At P 5, all cells were excitable and a majority discharged in tonic fashion. Ion conductances subserving maintenance of repetitive discharge were identifie d at P5 by exposure to low extracellular Ca2+, Cd2+, and charybdotoxin, all of which suppressed repetitive discharge. omega-Conotoxin GVIA and nifedip ine had no effect. We compared passive membrane properties and a variety of voltage-activated ion channels at E15 and P5. It was found that the densit y of high voltage-activated (HVA) Ca2+ currents increased in parallel with the development of repetitive firing, while the density of Ni2+-sensitive l ow voltage-activated (LVA) Ca2+ currents decreased. Changes in density and activation kinetics of tetrodotoxin-sensitive Na+ currents paralleled chang es in firing thresholds and size of action potentials, but seemed to be unr elated to maintenance of repetitive firing. Densities of A-type K+ currents and delayed rectifier currents did not change. The results suggest that HV A Ca2+ channels, and among them a toxin-resistant subtype, are specifically engaged in activation of Ca2+-sensitive K+ conductance and thereby account for frequency coding in postnatal RGNs. (C) 1999 John Wiley & Sons, Inc.