SK channels are expressed throughout the central nervous system. They are highly conserved in mammals as well as in other organisms such as Drosophila melanogaster and Caenorhabditis elegans. SK channels are specifically involved in the medium afterhyperpolarizing potential (mAHP). They affect both the intrinsic excitability of neurons and synaptic transmission. They are also involved in calcium signaling. SK channel activation can mediate neuroprotection in various models of cell death. SK channels control action potential discharge frequency in hippocampal neurons, midbrain dopaminergic neurons, dorsal vagal neurons, sympathetic neurons, nucleus reticularis thalamic neurons, inferior olive neurons, spinal and hypoglossal motoneurons, mitral cells in the olfactory bulb, and cortical neurons.