Pharmacology
Apamin binds to the SK channels (small conductance Ca2+-activated K+ channels) in the brain and spinal cord and inhibits them. It inhibits the three cloned SK channel subtypes (SK1, SK2, and SK3) with different affinity, highest affinity for SK2, lowest for SK1, and intermediate for SK3 channels. Heteromers show intermediate sensitivity. Most likely, apamin acts as a pore blocker, although residues both inside and outside of the pore region of the SK channels participate in apamin binding. The SK channels are present in a wide range of excitable and non-excitable cells, including cells in the central nervous system, intestinal myocytes, endothelial cells, and hepatocytes.
SK channels, when activated, contribute to afterhyperpolarizations in neurons, which control neuronal excitability. Intracellular Ca2+ binding to calmodulin can activate these channels. Channel deactivation can take place through dissociation of Ca2+ from calmodulin. Inhibition of SK channels by apamin will increase the neuronal excitability and lower the threshold for generating an action potential. Other toxins that block SK channels are tamapin and scyllatoxin.
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