Small conductance calcium-activated potassium channels (SK channels) serve a fundamental role in excitable cells. Activated by elevated levels of intracellular calcium, SK channels mediate the slow after hyperpolarization, the sAHP, which follows the action potential spike. During a sustained stimulus, a train of action potentials is elicited and the depth and extent of the sAHP are increased with each action potential such that the cell is ultimately unable to fire a subsequent action potential even though the stimulus to fire remains. This phenomenon is termed 'spike-frequency adaptation' and protects the cell from tetanic stimulation and associated cell toxicity. Subtypes of SK channels may be distinguished by different sensitivities to the bee venom peptide toxin apamin. Application of apamin to regions of the brain alters physiologically important processes, such as sleep patterns and learning and memory. While the sAHP in most neurons is apamin-sensitive, in some neurons such as hippocampal pyramidal cells, the sAHP is apamin-insensitive, shows a slower time course, and is modulated by activation of protein kinase A (PKA).
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