5‐HT1A receptors modulate small‐conductance Ca2+‐activated K+ channels

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Abstract
Small‐conductance calcium‐activated potassium channels (SK) are responsible for the medium afterhyperpolarisation (mAHP) following action potentials in neurons. Here we tested the ability of serotonin (5‐HT) to modulate the activity of SK channels by coexpressing 5‐HT1A receptors with different subtypes of SK channels (SK1, SK2, and SK3) in Xenopus laevis oocytes. SK channels were activated by intracellular injection of Cd2+. Subsequent activation of 5‐HT1A receptors by 8‐OH‐DPAT always produced an inhibition of the SK current, showing the existence of a specific pathway between the receptor and the ion channel. To investigate the physiological relevance of this pathway, we characterized the mAHP present after action potentials in spinal motoneurons recorded in a slice preparation from the lumbar spinal cord of the adult turtle. By performing current and voltage clamp recordings, we showed that 8‐OH‐DPAT specifically inhibited the fraction of the AHP mediated by SK channels. We conclude that the activity of SK channels is modulated by activation of serotonergic receptors.