Ca²⁺ mobilizing agents mimic serotonin 5-HT_2A facilitation of N-methyl-D-aspartate depolarization

Serotonin activation of 5-HT_2A receptors facilitates depolarization of neocortical neurons by N-methyl-D-aspartate (NMDA). Using grease-gap recordings from an in vitro cortical wedge preparation we have examined whether agents which raise the concentration of intracellular Ca²⁺ mimic the facilitation. Perfusing A23187, cyclopiazonic acid or thapsigargin selectively facilitate the NMDA depolarization of cortical neurons in a concentration-dependent manner. Buffering intracellular Ca²⁺ by perfusing BAPTA-AM eliminates the serotonin, cyclopiazonic acid and thapsigargin induced facilitation. We conclude that a rise in intracellular Ca²⁺ is both necessary and sufficient to account for facilitating the NMDA depolarization following activation of 5-HT_2A receptors.