K_V4.2 is a voltage-dependent K⁺ channel that belongs to the Shal channel subfamily and includes two other members: K_V4.1 and K_V4.3.¹

K_V4.2 possesses the signature structure of the voltage-dependent K⁺ channels: six membrane-spanning domains with intracellular N and C termini. As with other members of the voltage-gated K⁺ channel superfamily, the functional channel is a tetramer that can be composed of more than one member of the Shal subfamily, i.e. heterotetramers of K_V4.1 and K_V4.3.

The K_V4 channels are characterized by activation at subthreshold membrane potentials, inactivate rapidly and recover from inactivation quickly compared with other voltage-dependent K⁺ channels. This type of current is known as transient A-type K⁺ currents. For example, depolarization-activated K⁺ currents in rat neostriatal cholinergic interneurons are predominantly of the A-type and attributable to coexpression of K_V4.2 and K_V4.1 subunits.²

The biophysical properties of the K_V4.2 subunit can be modified by its association with auxiliary β subunits such as the KChIP family that increase K_V4.2 current densities and accelerates both the inactivation and the recovery time.

K_V4.2 is also highly expressed in the heart where together with K_V4.3 underlie the fast inactivating and recovering cardiac transient outward current I_to.³

Several toxins from spider venoms are potent blockers (affecting the channels in the nanomolar range) of K_V4.2 channels. Among these the most potent and selective are Stromatoxin-1 (#STS-350), (1.2nM), Phrixotoxin-1 (#STP-700), (5 nM), Phrixotoxin-2 (#STP-710), (34 nM) and Heteropodatoxin-2 (#STH-340), (100 nM).⁴