title: Diabetes alters protein expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits in rat nodose ganglion cells.
abstract: Vagal afferent neurons, serving as the primary afferent limb of the parasympathetic reflex, could be involved in diabetic autonomic neuropathy. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed in the vagal afferent neurons and play an important role in determining cell membrane excitation. In the present study, the protein expression and the electrophysiological characteristics of HCN channels were investigated in nodose ganglion (NG) afferent neurons (A-fiber and C-fiber neurons) from sham and streptozotocin (STZ)-induced diabetic rats. In the sham NG, HCN1, HCN3, and HCN4 were expressed in the A-fiber neurons; and HCN2, HCN3, and HCN4 were expressed in the C-fiber neurons. Compared to the sham NG neurons, diabetes induced the expression of HCN2 in the A-fiber neurons besides overexpression of HCN1 and HCN3; and enhanced the expression of HCN2 and HCN3 in C-fiber neurons. In addition, whole-cell patch-clamp data revealed diabetes also increased HCN currents in A-fiber and C-fiber neurons. However, we found that diabetes did not alter the total nodose afferent neuron number and the ratio of A-fiber/C-fiber neurons. These results indicate that diabetes induces the overexpression of HCN channels and the electrophysiological changes of HCN currents in the A- and C-fiber nodose neurons, which might contribute to the diabetes-induced alteration of cell excitability in the vagal afferent neurons.
authors.affiliation: Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, 68198, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: T P
authors.initials: TP
authors.lastname: Tran
authors.forename: R L
authors.initials: RL
authors.lastname: Muelleman
authors.forename: Y L
authors.initials: YL
authors.lastname: Li
mesh_terms: D000818:Animals; D002452:Cell Count; D000242:Cyclic AMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000096:biosynthesis; D021122:Protein Subunits / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D020033:Protein Isoforms; D021122:Protein Subunits; D000242:Cyclic AMP