K_V1.6 is a mammalian voltage-dependent K⁺ channel, homologous to the Drosophila Shaker K⁺ channel. K_V1.6 was first cloned from human 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_V1.6 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 other supporting cells in the brain, in cardiac and smooth muscle tissue as well as in ovary and testis² and its activity influences the membrane potential and excitability of expressing cells.

K_V1.6 channels are sensitive to low doses of TEA (7 mM) and high doses of 4-AP (1.5 mM), the “classical” non-selective potassium channel blockers.

Several toxins from snakes, scorpions and sea anemones venoms are potent blockers (affecting the channels in the nanomolar range) of K_V1.6 channels. Among these the most potent and selective are α-Dendrotoxin ((9-25 nM) and δ-Dendrotoxin (23 nM), Agitoxin-2 (0.036 nM), Hongotoxin-1 (6 nM), Margatoxin (5 nM) and Stichodactyla Toxin (0.16 nM).³