Kv1 potassium channel complexes in vivo require Kvbeta2 subunits in dorsal spinal neurons.

Whereas Kvbeta2 subunits modulate potassium current properties carried by Kv1 channel complexes in heterologous systems, little is known about the contributions of Kvbeta2 subunits to native potassium channel function. Using antisense approaches and in situ recordings from Xenopus embryo spinal cord neurons, we tested the in vivo roles of Kvbeta2 subunits in modulation of voltage-dependent potassium current (IKv). We focused on 1) two different populations of dorsal spinal neurons that express both Kvbeta2 and Kv1 alpha-subunit genes and 2) the 24- and 48-h developmental period, during which IKv undergoes developmental regulation.

Localization of Kv2.2 protein in Xenopus laevis embryos and tadpoles.

Voltage-gated potassium (Kv) channels sculpt neuronal excitability and play important developmental roles. Kv channels consist of pore-forming alpha- and auxiliary subunits. For many Kv alpha-subunits, existing mRNA probes and antibodies have allowed analysis of expression patterns, typically during adult stages.

Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development.

In addition to rapid signaling, electrical activity provides important cues to developing neurons. Electrical activity relies on the function of several different types of voltage-gated ion channels. Whereas voltage-gated Ca2+ channel activity regulates several aspects of neuronal differentiation, much less is known about developmental roles of voltage-gated Na+ channels, essential mediators of electrical signaling.

Gene duplications and evolution of vertebrate voltage-gated sodium channels.

Voltage-gated sodium channels underlie action potential generation in excitable tissue. To establish the evolutionary mechanisms that shaped the vertebrate sodium channel alpha-subunit (SCNA) gene family and their encoded Nav1 proteins, we identified all SCNA genes in several teleost species. Molecular cloning revealed that teleosts have eight SCNA genes, compared to ten in another vertebrate lineage, mammals.

Embryonic and larval expression of zebrafish voltage-gated sodium channel alpha-subunit genes.

Whereas it is known that voltage-gated calcium channels play important roles during development, potential embryonic roles of voltage-gated sodium channels have received much less attention. Voltage-gated sodium channels consist of pore-forming alpha-subunits (Na(v)1) and auxiliary beta-subunits. Here, we report the embryonic and larval expression patterns for all eight members of the gene family (scna) coding for zebrafish Na(v)1 proteins.

Carboxyl tail region of the Kv2.2 subunit mediates novel developmental regulation of channel density.

Molecular mechanisms underlying the acquisition of stable electrical phenotypes in developing neurons remain poorly defined. As Xenopus embryonic spinal neurons mature, they initially exhibit dramatic changes in excitability due to a threefold increase in voltage-gated potassium current (IKv) density. Later when mature neurons begin synapse formation, IKv density remains stable.

In vivo analysis of Kvbeta2 function in Xenopus embryonic myocytes.

Kv1 potassium channels consist of pore-forming alpha subunits as well as auxiliary beta subunits. In heterologous systems, Kv1alpha subunits suffice for induction of voltage-dependent potassium current (I(Kv)). Although Kv1 channels can be expressed without auxiliary subunits in heterologous systems, coexpression with Kvbeta subunits has dramatic effects on surface expression and kinetic properties.