K_V1.2 is a mammalian voltage-dependent K⁺ channel, homologous to the Drosophila Shaker K⁺ channel. K_V1.2 was first cloned from rat brain.¹ Eight Shaker-related genes exist in mammals constituting the K_V1 subfamily of the large K_V channel family of genes.²

A functional K_V1 channel is either a membrane spanning homotetramer or heterotetramer, which is composed of members of the same subfamily. In addition several auxiliary subunits and intracellular proteins might interact with the channel and affect its function.

The structure of K_V1.2 channel is similar to all K_V channels and includes six membrane spanning helices creating a voltage sensor domain and a pore domain.²

The channel is expressed in neurons and cardiac and smooth muscle tissue as well as in retina and pancreas.² The crystal structure of K_V1.2 was recently solved shading light on the structure of a mammalian voltage dependent channel.³ The functional channel is considered low voltage activated and shows very little inactivation. Therefore, this channel activity influences the membrane potential and excitability of neurons and muscle.

K_V1.2 channels are sensitive to high doses of TEA (560 mM) and low doses of 4-AP (0.59 mM), the “classical” non-selective potassium channel blockers.

Several venomous toxins from snakes, scorpions and honey bee are potent blockers (affecting the channels in the nanomolar range) of K_V1.2 channels. Among these, the most potent and selective are α-Dendrotoxin (1-12 nM), Dendrotoxin-I (0.13 nM), Maurotoxin (0.1-0.8 nM), Hongotoxin-1 (0.17 nM), Margatoxin (0.16-0.65 nM), Tityustoxin Kα (0.21 nM) and MCD peptide (10-400 nM).⁴