Small conductance calcium-activated potassium channel protein 2 (SK2) (SK2)

Small conductance calcium-activated potassium channel protein 2 (SK2), encoded by the KCNN2 gene, is a voltage-independent potassium channel that opens in response to increases in intracellular calcium levels [UniProt: P58335]. It is widely expressed in the central nervous system and the heart, where it plays a pivotal role in regulating membrane potential and excitability [PMID: 25635011]. In neurons, SK2 channels contribute to the medium afterhyperpolarization (mAHP), which limits the frequency of action potential firing and influences synaptic plasticity and long-term potentiation [PMID: 30104295]. In the heart, SK2 channels are predominantly expressed in the atria and contribute to the repolarization phase of the action potential [PMID: 21411614]. Dysregulation of SK2 channel activity is implicated in various pathologies, including atrial fibrillation, epilepsy, and neurodegenerative diseases like Parkinson's and Alzheimer's [PMID: 25635011]. Consequently, SK2 is a significant therapeutic target, with research focusing on both activators (positive allosteric modulators) for treating hyperexcitability disorders and inhibitors for managing cardiac arrhythmias [IUPHAR: KCa2.2].

Other names

KCa2.2SKCA2hSK2KCNN2Small conductance calcium-activated potassium channel 2

Positive allosteric modulation of channel opening; Pore blockade inhibiting potassium efflux; Negative allosteric modulation reducing calcium sensitivity [IUPHAR, PMID: 25635011]