Figure 1:

Ion channels that contribute to the human β-cell action potential. Glucose is taken up and metabolized in β-cells resulting in both an increase in the ATP/ADP ratio as well as cell swelling. The increase in the ATP/ADP ratio leads to K_ATP closure whereas swelling activates SWELL-1 Cl^- efflux. Reduced K_ATP activity together with the depolarizing influences of SWELL1 mediated Cl^- efflux and Na⁺ influx through Na⁺ leak channels results in V_m depolarization. V_m depolarization activates voltage-dependent Ca²⁺ channels (VDCCs) and voltage-gated Na⁺ channels (VGSCs) that are responsible for the upstroke of the action potential (AP); a representative human β-cell AP is shown on the right side of the β-cell. The rapid V_m depolarization as well as Ca²⁺ entry that occurs during the AP upstroke activates K⁺ channels including BK, K_V, SK and IK. BK channels are voltage and calcium activated, which provide the largest conductance and fastest activating K⁺ current that is responsible for the initiation of AP repolarization. K_V channels are activated by V_m depolarization and also contribute to AP repolarization. Finally, the Ca²⁺ activated K⁺ channels including SK and IK are smaller conductance K⁺ currents that stay active for longer following AP repolarization leading to afterhyperpolarization and a reduction in AP frequency.