Kv3 channels

Analysis of the Kv3 subfamily of K+ channel subunits has lead to the discovery of a new class of neuronal voltage-gated K+ channels characterized by positively shifted voltage dependencies and very fast deactivation rates. These properties are adaptations that allow these channels to produce currents that can specifically enable fast repolarization of action potentials without compromising spike initiation or height. The short spike duration and the rapid deactivation of the Kv3 currents after spike repolarization maximize the quick recovery of resting conditions after an action potential.

The ability to fire action potentials at high frequencies (often up to 1 kHz) or to follow high-frequency inputs are important physiological functions of numerous cells throughout the mammalian CNS. Neuronal populations within such disparate regions as the hippocampus, basal ganglia, neocortex, reticular thalamus, medial vestibular nucleus and auditory nuclei are capable of responding to afferent input with action potentials of brief duration and of firing repetitively at high frequencies.

Although numerous channel types have been implicated in conferring such properties, the voltage-gated K+ channels of the Kv3 subfamily have now been identified as major determinants of the FS phenotype.

Molecular characteristics of Kv3 subfamily members
Both rodents and humans possess four Kv3 genes: Kv3.1, Kv3.2, Kv3.3 and Kv3.4 ([6 and 7]). All four Kv3 genes generate multiple protein isoforms by alternative splicing, which produces versions with different intracellular C-terminal sequences. There are now 13 different Kv3 proteins known in mammals (Kv3.1a–Kv3.1b, Kv3.2a–Kv3.2d, Kv3.3a–Kv3.3d and Kv3.4a–Kv3.4c), yet the currents expressed in heterologous expression systems by the spliced isoforms of each Kv3 gene are virtually indistinguishable. Recent studies suggest that the alternatively spliced C termini confer isoform-specific regulation by second messenger signaling systems and targeting to distinct neuronal compartments.