Voltage-gated K⁺ (Kv) channels are potassium selective multimeric channels that change their conformation in response to changes in the membrane potential. Kv channels play a central role in the determination of cellular excitability due to their contribution to the shape, duration and frequency of action potentials. A wide range of physiological activities are regulated via K_V actions including cell signaling, proliferation and migration¹.

Kv channels are divided into several subfamilies based in sequence homology.  Members of the Kv5, Kv6, Kv8, and Kv9 subfamilies, are unable to form functional channels, even though they have the typical topology of a Kv α-subunit and have therefore been designated silent Kv (KvS) subunits. 

K_V6.4 (also known as KCNG4) is part of the electrically silent K_V6 subfamily that includes four members Kv6.1-Kv6.4². Members of the Kv6 subfamily selectively interact with members of the Kv2 subfamily, forming functional Kv2/KvS heterotetramers that possess unique biophysical and pharmacological properties ². 

Heterotetramerization of K_V6.4 with Kv2 results in the formation of functional channels. The stoichiometry of Kv2/Kv6 complex was recently found to be 2:2 stoichiometry with activation V_1/2 of 5.7 ± 3.1 mV and inactivation V_1/2 of -62.8 ± 1.6 mV³.