K2.3 is found in the central nervous system (CNS), muscle, liver, pituitary, prostate, kidney, pancreas and vascular endothelium tissues. K2.3 is most abundant in regions of the brain, but has also been found to be expressed in significant levels in many other peripheral tissues, particularly those rich in smooth muscle, including the rectum, corpus cavernosum, colon, small intestine and myometrium.
The expression level of KCNN3 is dependent on hormonal regulation, particularly by the sex hormone estrogen. Estrogen not only enhances transcription of the KCNN3 gene, but also affects the activity of K2.3 channels on the cell membrane. In GABAergic preoptic area neurons, estrogen enhanced the ability of α1 adrenergic receptors to inhibit K2.3 activity, increasing cell excitability. Links between hormonal regulation of sex organ function and K2.3 expression have been established. The expression of K2.3 in the corpus cavernosum in patients undergoing estrogen treatment as part of gender reassignment surgery was found to be increased up to 5-fold. The influence of estrogen on K2.3 has also been established in the hypothalamus, uterine and skeletal muscle.