Hyperpolarization-activated, cyclic nucleotide-gated cation channels: roles in the differential electrophysiological properties of rat primary afferent neurons.
The large, medium-sized, and small neurons of the dorsal root ganglion (DRG) have different functions in the processing of various senses. Hyperpolarization-activated, cyclic nucleotide-gated channels (HCN) contribute greatly to neuronal excitability. In the present study, which used whole-cell patch clamp techniques and immunohistochemical staining methods, the electrophysiological properties of DRG neurons were systematically compared, and the roles of HCN-1, -2, and -4 were examined. The main results were as follows. 1) The large neurons had significantly higher V0.5 values (membrane potential at which the HCN channels were half-activated) and shorter time constants (tau) than small or medium-sized DRG neurons. However, large DRG neurons had higher Ih density (HCN neuron current). 2) HCN-1 was found predominantly, but not exclusively, in large and medium-sized DRG neurons; HCN-2 was found in all DRG neurons; and HCN-4 was poorly visualized in all DRG neurons. HCN-1 and HCN-2 were colocalized in large and medium-sized neurons with immunostaining of adjacent sections. In the dorsal horn of the spinal cord, HCN-1, HCN-2, and HCN-4 were all expressed in laminae I-IV, although HCN-1 was not detectable in lamina II. 3) Blockade of Ih current in DRG neurons caused a significant decrease in V0.5, resting membrane potential, and repetitive firing number of action potential and a significant increase in time of rising phase of action potential. These results suggest that the different HCN channels in the three types of DRG neurons might contribute to their differential electrophysiological properties.
Tu
Huiyin
H
Neuroscience Research Institute, Peking University, Key Laboratory of Neuroscience (Peking University), Ministry of Education, Beijing, Peoples Republic of China.
Deng
Lunbin
L
Sun
Qian
Q
Yao
Lei
L
Han
Ji-Sheng
JS
Wan
You
Y
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D002478:Cells, Cultured; D054815:Cyclic Nucleotide-Gated Cation Channels; D004558:Electric Stimulation / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology*; D006023:Glycoproteins / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D037102:Lectins / Q000378:metabolism; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000145:classification / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D053675:Versicans
D054815:Cyclic Nucleotide-Gated Cation Channels; D006023:Glycoproteins; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D037102:Lectins; D016900:Neurofilament Proteins; D015221:Potassium Channels; D011743:Pyrimidines; C508324:Vcan protein, rat; D053675:Versicans; C082246:ICI D2788