The 5-HT(4) 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 Ih, a hyperpolarization-activated cation current. In contrast, we find no evidence for the involvement of Ih in this response. Rather, this depolarization may involve a cyclic nucleotide gated channel.
Chapin
Esther M
EM
Cellular and Clinical Neurobiology Training Program, Wayne State University School of Medicine, 2309 Scott Hall, 540 E Canfield, Detroit, MI 48201, USA.
Haj-Dahmane
Samir
S
Torres
Gonzalo
G
Andrade
Rodrigo
R
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002412:Cations / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002412:Cations; D004791:Enzyme Inhibitors; D007473:Ion Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases