K_Ca2.3 (KCNN3, SK3) is a member of the Ca²⁺-activated K⁺ channel family with small conductance that includes K_Ca2.1 (KCNN1, SK1) and K_Ca2.2 (KCNN2, SK2). The channel is voltage insensitive and is activated by intracellular Ca²⁺ in the submicromolar range. It has, though, a similar topology to that of voltage-dependent K⁺ channels (K_V channels), that is six transmembrane domains and intracellular N- and C-termini. The functional channel of all the K_Ca2 family members is a multimeric protein composed of four pore-forming subunits.

K_Ca2 channels are extremely sensitive to the levels of intracellular Ca²⁺ and concentrations as low as 300-700 nM can open the channels very rapidly (5-15 ms). Hence, the K_Ca2 channels are highly sensitive and fast Ca²⁺ sensors resembling other known Ca²⁺-binding proteins. This type of Ca²⁺-dependent activation is achieved by the constitutive binding of the K_Ca2 channels to calmodulin, a highly expressed Ca²⁺-binding protein via a calmodulin-binding domain situated at the cytoplasmic C-terminus.

Pharmacologically, the K_Ca2 channels are the only known targets of the bee venom toxin Apamin, with K_Ca2.1 being the least sensitive, K_Ca2.2 the most sensitive and K_Ca2.3 showing intermediate sensitivity.

K_Ca2.3 is predominantly expressed in the nervous system although expression in endothelial cells, heart and liver have been described.

K_Ca2.3 is known to be involved in the regulation of neuronal excitability. They do so mainly via a phenomenon known as after hyperpolarization in which K_Ca2 channels open in response to increased intracellular Ca²⁺ concentrations that result from the entry of extracellular Ca²⁺ through voltage-dependent Ca²⁺ channels during action potentials. In this way, K_Ca2 channels effectively form a Ca²⁺-mediated feedback loop.

K_Ca2.3 is involved in the control of firing rate and subsequent dopamine secretion from midbrain dopaminergic neurons. Since malfunction of these neurons is involved in several pathological disorders such as Parkinson’s disease and Schizophrenia, modulators of the K_Ca2.3 channels have been proposed to be of therapeutic value in these diseases.