KCNN2

KCNN2 is the gene that encodes the small-conductance calcium-activated potassium channel subunit SK2, also known as KCa2.2. It is part of the family of small-conductance Ca2+-activated K+ channels, which includes KCNN1 and KCNN3.

SK2 channels are activated by intracellular calcium through calmodulin, which is constitutively bound to the channel's C-terminal region. Upon Ca2+ binding, the channel opens and mediates K+ efflux, contributing to membrane hyperpolarization. The channel is typically formed as a tetramer, with each subunit spanning six transmembrane segments and contributing to a central pore.

In neurons, SK2 channels contribute to the medium afterhyperpolarization that follows action potentials, helping regulate firing rate, spike-frequency adaptation, and synaptic integration. They are widely expressed in brain regions such as the hippocampus, cortex, and cerebellum, and are implicated in processes related to learning and memory and in regulating dendritic excitability.

Pharmacologically, SK channels are inhibited by the bee venom peptide apamin, with SK2 showing a characteristic potency profile. Positive modulators, including CyPPA and EBIO, can enhance SK2 activity and are used experimentally to study channel function.

Clinical significance and research relevance: alterations in KCNN2 function or expression can affect neuronal excitability and synaptic plasticity, with potential relevance to cognitive disorders, epilepsy, and mood regulation. KCNN2 remains a focus of research for therapeutic strategies aimed at modulating neuronal excitability via SK2.

Alternate names for the gene product include KCa2.2 and SK2.