The 5-HT₄ receptor-induced depolarization in rat hippocampal neurons is mediated by cAMP but is independent of I_h

Intracellular recordings were used to examine the mechanisms underlying the 5-hydroxytryptamine (5-HT)₄ receptor-mediated depolarization seen in CA1 region pyramidal cells in in vitro hippocampal brain slices. This depolarization was mimicked and occluded by administration of the membrane permeable cyclic adenosine monophosphate (cAMP) analog 8-bromo-cAMP but was unaffected by blockade of protein kinase A (PKA). These results suggest that 5-HT₄ receptors signal this depolarization through a cAMP-dependent but PKA-independent mechanism. In many cell types, 5-HT elicits a depolarization via cAMP by facilitating I_h, a hyperpolarization-activated cation current. In contrast, we find no evidence for the involvement of I_h in this response. Rather, this depolarization may involve a cyclic nucleotide gated channel.