Differential modulation of I(h) by 5-HT receptors in mouse CA1 hippocampal neurons.
CA1 pyramidal neurons of the hippocampus express various types of serotonin (5-HT) receptors, such as 5-HT(1A), 5-HT(4) and 5-HT(7) receptors, which couple to Galpha(i) or Galpha(s) proteins and operate on different intracellular signalling pathways. In the present paper we verify such differential serotonergic modulation for the hyperpolarization-activated current I(h). Activation of 5-HT(1A) receptors induced an augmentation of current-induced hyperpolarization responses, while the responses declined after 5-HT(4) receptors were activated. The resting potential of neurons hyperpolarized (-2.3 +/- 0.7 mV) after 5-HT(1A) receptor activation, activation of 5-HT(4) receptors depolarized neurons (+3.3 +/- 1.4 mV). Direct activation of adenylyl cyclase (AC) by forskolin also produced a depolarization. In voltage clamp, the Ih current was identified by its characteristic voltage- and time-dependency and by blockade with CsCl or ZD7288. Activation of 5-HT(1A) receptors reduced I(h) and shifted the activation curve to a more negative voltage by -5 mV at half-maximal activation. Activation of 5-HT(4) and 5-HT(7) receptors increased I(h) and shifted the activation curve to the right by +5 mV. Specific activation of 5-HT(4) receptors by BIMU8 increased membrane conductance and showed an increase in I(h) in a subset of cells, but did not induce a significant alteration in the activation curve. In order to verify spatial differences, we applied BIMU8 selectively to the soma and to the dendrites. Only somatic application induced receptor activation. These data are confirmed by immunofluorescence stainings with an antibody against the 5-HT(4) receptor, revealing receptor expression at the somata of the CA1 region. A similar expression pattern was found with a new antibody against 5-HT(7) receptors which reveals immunofluorescence staining on the cell bodies of pyramidal neurons.
Bickmeyer
Ulf
U
Abteilung Neuro- und Sinnesphysiologie, Georg-August Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
Heine
Martin
M
Manzke
Till
T
Richter
Diethelm W
DW
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D007473:Ion Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin