1.A.1.16.7
Small conductance calcium-activated potassium channel protein 3 of 736 aas and 6 TMSs, SK3 or KCNN3. It forms a voltage-independent potassium channel, activated by intracellular calcium (Bauer et al. 2019). Activation is followed by membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic after-hyperpolarization. The channel is blocked by apamin. Contrary to its bradycardic effect in the sinus node, blockage of its current by apamin accelerates ventricular automaticity and causes repeated, nonsustained, ventricular tachycardia in normal ventricles. Ryanodine receptor 2 blockage reversed the apamin effects on ventricular automaticity (Wan et al. 2019). Dextran sodium sulfate treatment causes loss of transient relaxation due to downregulation of SK3 channels and may increase contractile responses due to increased Ca²⁺ sensitization of smooth muscle cells via protease-activated receptor_1 (PAR1) [TC# P25116; TC# 9.A.14.13.37] activation (Sung et al. 2022). The specificity of Ca²⁺-activated K⁺ channel modulation in atherosclerosis and aerobic exercise training has been discussed (Mokelke et al. 2022).  Small conductance calcium-activated potassium (SK) channel-positive modulators prevent ferroptosis and excitotoxicity in neuronal cells (Zhang et al. 2024).