KCNN3

KCNN3, also known as KCNN3 gene or by the protein name SK3 (small-conductance calcium-activated potassium channel 3) or KCa2.3, encodes a pore-forming subunit of small-conductance calcium-activated potassium channels. It is a member of the KCNN family, which also includes KCNN1 (SK1) and KCNN2 (SK2). The KCNN3 gene product forms functional channels that can assemble as homotetramers or as heteromeric channels with other SK subunits, leading to variations in biophysical properties and pharmacology.

The SK3 channel is activated by intracellular calcium via constitutively bound calmodulin, providing a direct link between Ca2+ signaling and membrane excitability. Once opened, SK3 channels conduct potassium efflux, contributing to the medium afterhyperpolarization and helping to regulate neuronal firing rate, patterns, and synaptic plasticity. Expression of KCNN3 is notable in various brain regions, including cortex and hippocampus, and it is found in some peripheral tissues as well.

Pharmacologically, SK channels are inhibited by the peptide toxin apamin, with effects influenced by subunit composition. Modulators such as certain openers (for example, EBIO and related compounds) can enhance SK channel activity, providing research tools and potential therapeutic avenues.

Clinical and research significance varies; altered KCNN3 expression or function has been studied in several neurological and psychiatric contexts, including epilepsy, schizophrenia, and Parkinson’s disease, though findings are not yet conclusive. Due to their role in shaping excitability and plasticity, SK3 channels remain a topic of interest for understanding neural computation and exploring targeted modulation of neural activity.