title: Postnatal maturation of the hyperpolarization-activated cation current, I(h), in trigeminal sensory neurons.
abstract: Hyperpolarization-activated inward currents (I(h)) contribute to neuronal excitability in sensory neurons. Four subtypes of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate I(h), with different activation kinetics and cAMP sensitivities. The aim of the present study was to examine the postnatal development of I(h) and HCN channel subunits in trigeminal ganglion (TG) neurons. I(h) was investigated in acutely dissociated TG neurons from rats aged between postnatal day (P)1 and P35 with whole cell patch-clamp electrophysiology. In voltage-clamp studies, I(h) was activated by a series of hyperpolarizing voltage steps from -40 mV to -120 mV in -10-mV increments. Tail currents from a common voltage step (-100 mV) were used to determine I(h) voltage dependence. I(h) activation was faster in older rats and occurred at more depolarized potentials; the half-maximal activation voltage (V(1/2)) changed from -89.4 mV (P1) to -81.6 mV (P35). In current-clamp studies, blocking I(h) with ZD7288 caused membrane hyperpolarization and increases in action potential half-duration at all postnatal ages examined. ZD7288 also reduced the action potential firing frequency in multiple-firing neurons. Western blot analysis of the TG detected immunoreactive bands corresponding to all HCN subtypes. HCN1 and HCN2 band density increased with postnatal age, whereas the low-intensity HCN3 and moderate-intensity HCN4 bands were not changed. This study suggests that functional I(h) are activated in rat trigeminal sensory neurons from P1 during postnatal development, have an increasing role with age, and modify neuronal excitability.
authors.affiliation: Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Jennings
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D008969:Molecular Sequence Data; D059225:Nociception / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D021122:Protein Subunits; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C513835:HCN3 protein, rat; C513836:HCN4 protein, rat; C578667:Hcn1 protein, rat; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D021122:Protein Subunits; D011743:Pyrimidines; C082246:ICI D2788