Blunted excitability of aortic baroreceptor neurons in diabetic rats: involvement of hyperpolarization-activated channel

• Published in: Cardiovascular research Vol. 79; no. 4; pp. 715 - 721
• Main Authors: Li, Yu-Long, Tran, Thai Paul, Muelleman, Robert, Schultz, Harold D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2008
• Subjects: Action Potentials; Animals; Aorta - innervation; Autonomic nervous system; Baroreflex; Biological and medical sciences; Cardiology. Vascular system; Cesium - pharmacology; Chlorides - pharmacology; Cyclic AMP - metabolism; Cyclic Nucleotide-Gated Cation Channels - antagonists & inhibitors; Cyclic Nucleotide-Gated Cation Channels - metabolism; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Electrophysiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Ion channels; Ion Channels - metabolism; Male; Medical sciences; Nerve Fibers, Myelinated - metabolism; Nodose Ganglion - metabolism; Nodose Ganglion - physiopathology; Potassium Channels - metabolism; Pressoreceptors - drug effects; Pressoreceptors - metabolism; Pressoreceptors - physiopathology; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; Time Factors; Up-Regulation; Electrophysiology; Ion channels; Diabetes; Autonomic nervous system; Baroreflex; Endocrinopathy; Rat; Diabetes mellitus; Rodentia; Excitability; Ionic channel; Phlebology; Vertebrata; Mammalia; Neuron; Animal; Aorta; Circulatory system; Baroreceptor; Cardiology; Hyperpolarization
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvn141

Aims Although dysfunction of arterial baroreflex occurs in human and animal models of type-1 diabetes (T1D), the mechanisms involved in the impairment of the baroreflex still remain unclear. The nodose ganglion (NG) contains the cell bodies of the aortic baroreceptor (AB) neurons. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed in AB neurons and play an important role in regulating the cell excitability. We investigated whether the excitability of AB neurons is depressed in streptozotocin (STZ)-induced T1D rats and whether HCN channels are involved in this depression. Methods and results Using the whole-cell patch clamp technique, we found that AB neuron excitability (action potential frequency at 50 pA current stimulation) in the T1D rats was lower than that in the sham rats (0.4 ± 0.5 vs. 4.8 ± 0.6 spikes/s, P < 0.05; AB neurons were identified by DiI staining). In addition, HCN current density in AB neurons from the T1D rats was bigger than that from the sham rats (60.2 ± 6.1 vs. 30.7 ± 4.9 pA/pF at test pulse −140 from holding potential −40 mV, P < 0.05). Furthermore, HCN channel blockers (5 mM cesium chloride and 100 µM ZD7288) significantly reduced HCN currents and increased action potential frequency of the AB neurons in sham and T1D rats. Immunofluorescent and western blot analyses demonstrated that the expression of HCN1 and HCN2 channel protein in the NG from the T1D rats was higher than that from the sham rats. Conclusion These results indicate that the HCN channels influence the excitability of AB neurons, and more importantly, contribute to the decreased excitability of AB neurons in T1D rats.