K_V1.4 is a mammalian voltage-dependent K⁺ channel, homologous to the Drosophila Shaker K⁺ channel. K_V1.4 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_V1.4 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 pancreas.² The functional channel is considered transient (A-type) current and shows pronounced inactivation. Therefore, this channel activity influences the membrane potential and excitability of neurons and muscle.

K_V1.4 channels are sensitive to high doses of TEA (>100 mM) and low doses of 4-AP (0.013 mM), the “classical” non-selective potassium channel blockers.

Most venomous peptide toxins that affect other K_V channels do not inhibit K_V1.4. However, the sea anemone toxin Stichodactyla Toxin (ShK), which is more potent towards K_V1.1 and K_V1.3, is still a potent inhibitor of K_V1.4 channels.³