DIFFERENTIAL EXPRESSION OF K4-AP CURRENTS AND KV3.1 POTASSIUM CHANNELTRANSCRIPTS IN CORTICAL-NEURONS THAT DEVELOP DISTINCT FIRING PHENOTYPES

Maturation of electrical excitability during early postnatal developme nt is critical to formation of functional neural circuitry in the mamm alian neocortex. Little is known, however, about the changes in gene e xpression underlying the development of firing properties that charact erize different classes of cortical neurons, Here we describe the deve lopment of cortical neurons with two distinct firing phenotypes, regul ar-spiking (RS) and fast-spiking (FS), that appear to emerge from a po pulation of immature multiple-spiking (IMS) neurons during the first t wo postnatal weeks, both in vivo (within layer IV) and in vitro. We re port the expression of a slowly inactivating, 4-AP-sensitive potassium current (K4-AP) at significantly higher density in FS compared with R S neurons. The same current is expressed at intermediate levels in IMS neurons. The kinetic, voltage-dependent, and pharmacological properti es of the K4-AP current are similar to those observed by heterologous expression of Kv3.1 potassium channel mRNA. Single-cell RT-PCR analysi s demonstrates that PCR products representing Kv3.1 transcripts are am plified more frequently from FS than RS neurons, with an intermediate frequency of Kv3.1 detection in neurons with immature firing propertie s. Taken together, these data suggest that the Kv3.1 gene encodes the K4-AP, current and that expression of this gene is regulated in a cell -specific manner during development. Analysis of the effects of 4-AP o n firing properties suggests that the K4-AP current is important for r apid action potential repolarization, fast after-hyperpolarization, br ief refractory period, and high firing frequency characteristic of FS GABAergic interneurons.