K_V1.1 is a mammalian voltage-dependent K⁺ channel, homologous to the Drosophila Shaker K⁺ channel. K_V1.1 was the first mammalian K_V channel to be cloned from mouse 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_V1.1 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 skeletal muscle tissue as well as in the retina and pancreas.² 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. Mutations in the coding of K_V1.1 gene were discovered in Episodic Ataxia patients.³

K_V1.1 channels are sensitive to low doses of TEA (0.3 mM) and 4-AP (0.29 mM), the “classical” non-selective potassium channel blockers.

Several venomous toxins from snakes, scorpions and sea anemones are potent blockers (affecting the channels in the nanomolar range) of K_V1.1 channels. Among these, the most potent and selective are α-Dendrotoxin (0.4-4 nM) and δ-Dendrotoxin (0.03-1.8 nM), Dendrotoxin-K (0.03 nM), Agitoxin-2 (0.044 nM) and Hongotoxin-1 (0.031 nM).⁴