Serotonergic modulation of hyperpolarization-activated current in acutely isolated rat dorsal root ganglion neurons.
1. The effect of serotonin (5-HT) on the hyperpolarization-activated cation current (IH) was studied in small-, medium- and large-diameter acutely isolated rat dorsal root ganglion (DRG) cells, including cells categorized as type 1, 2, 3 and 4 based on membrane properties. 5-HT increased IH in 91 % of medium-diameter DRG cells (including type 4) and in 67 % of large-diameter DRG cells, but not other DRG cell types. 2. The increase of IH by 5-HT was antagonized by spiperone but not cyanopindolol, and was mimicked by 5-carboxyamidotryptamine, but not (+)-8-hydroxydipropylaminotetralin (8-OH-DPAT) or cyanopindolol. These data suggested the involvement of 5-HT7 receptors, which were shown to be expressed by medium-diameter DRG cells using RT-PCR analysis. 3. 5-HT shifted the conductance-voltage relationship of IH by +6 mV without changing peak conductance. The effects of 5-HT on IH were mimicked and occluded by forskolin, but not by inactive 1,9-dideoxy forskolin. 4. At holding potentials negative to -50 mV, 5-HT increased steady-state inward current and instantaneous membrane conductance (fast current). The 5-HT-induced inward current and fast current were blocked by Cs+ but not Ba2+ and reversed at -23 mV, consistent with the properties of tonically activated IH. 5. In medium-diameter neurons recorded from in the current clamp mode, 5-HT depolarized the resting membrane potential, decreased input resistance and facilitated action potential generation by anode-break excitation. 6. The above data suggest that in distinct subpopulations of DRG neurons, 5-HT increases cAMP levels via activation of 5-HT7 receptors, which shifts the voltage dependence of IH to more depolarized potentials and increases neuronal excitability.
Cardenas
C G
CG
Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, TN 38163, USA.
Mar
L P
LP
Vysokanov
A V
AV
Arnold
P B
PB
Cardenas
L M
LM
Surmeier
D J
DJ
Scroggs
R S
RS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D048429:Cell Size; D054815:Cyclic Nucleotide-Gated Cation Channels; D018492:Dopamine Antagonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D015221:Potassium Channels; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology
D054815:Cyclic Nucleotide-Gated Cation Channels; D018492:Dopamine Antagonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D012701:Serotonin; C047975:cyanopindolol; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D010869:Pindolol