Small-conductance calcium-activated potassium channel (SK channel) (SK channel)

Small-conductance calcium-activated potassium (SK) channels are a family of ion channels (KCa2.1, KCa2.2, KCa2.3) that play a fundamental role in regulating cellular excitability by coupling intracellular calcium signaling to membrane potential (Adelman et al., 2012, PubMed: 22229574). These channels are unique because they are voltage-independent and are gated by calcium through the constitutive binding of calmodulin to their C-terminal domain (Fanger et al., 2001, PubMed: 11160633). In the central nervous system, SK channels mediate the medium afterhyperpolarization (mAHP) following an action potential, which limits the frequency of neuronal firing and influences synaptic plasticity and memory formation (Stockton et al., 2014, PubMed: 24501277). Beyond the brain, SK channels are significantly expressed in the heart, particularly in the atria, where they contribute to repolarization; their dysregulation is a known factor in the pathogenesis of atrial fibrillation (Zhang et al., 2015, PubMed: 25613814). Therapeutic interest in SK channels is high, with research focusing on positive allosteric modulators for treating ataxia and epilepsy, and inhibitors for managing cardiac arrhythmias (Weatherall et al., 2010, PubMed: 20634304). However, drug development faces challenges regarding subtype selectivity and the potential for central nervous system side effects or pro-arrhythmic risks (Liegeois et al., 2003, PubMed: 12691163).

Other names

SKCaKCa2KCNNSmall-conductance calcium-activated K+ channelKCNN1KCNN2KCNN3KCa2.1KCa2.2KCa2.3

Positive allosteric modulation of calcium sensitivity or direct pore blockade to modulate potassium conductance and regulate membrane hyperpolarization (Adelman et al., 2012, PubMed: 22229574).