Silent Kv subunits as major players in cell membrane excitability

Abstract

Silent Kv subunits are alpha subunits forming heteromeric Kv channels. These subunits do not form functional homomeric Kv channels, and their function in cell biology is realized when co-assembled with Kv2 subunits. There are currently 10 silent Kv subunits encoded in the genome of humans and other mammals, and they all produce biophysically unique voltage-gated potassium channels. KvS subunits are expressed in various tissues in the body, with tissue-specific distribution in many cases, where they fine tune cell excitability to keep homeostasis in health and disease. There are currently over 400 genome-wide association studies involving KvS subunits with traits and diseases. Although some statistics methods suggest parsimony when interpreting these populational data, it is undeniable that KvS-subunit-encoding genes, conserved part of the DNA, have important roles in biology. KvS subunits are unexplored as molecular targets. This perspective paper proposes to serve as a valuable resource for upcoming, detailed studies of these heteromeric channels, particularly focusing on the gating-related molecular mechanisms of the KvS subunits.