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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)715-721
Number of pages7
JournalCardiovascular research
Volume79
Issue number4
DOIs
StatePublished - Sep 1 2008

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Pressoreceptors
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Type 1 Diabetes Mellitus
Neurons
Nodose Ganglion
Baroreflex
Cyclic Nucleotides
Action Potentials
Patch-Clamp Techniques
Streptozocin
Animal Models
Western Blotting
Staining and Labeling

Keywords

  • Autonomic nervous system
  • Baroreflex
  • Diabetes
  • Electrophysiology
  • Ion channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

@article{1ecdb7a7a8ba415bbd10396e5ec9f241,
title = "Blunted excitability of aortic baroreceptor neurons in diabetic rats: Involvement of hyperpolarization-activated channel",
abstract = "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.",
keywords = "Autonomic nervous system, Baroreflex, Diabetes, Electrophysiology, Ion channels",
author = "Yulong Li and Tran, {Thai Paul} and Muelleman, {Robert Leo} and Schultz, {Harold D}",
year = "2008",
month = "9",
day = "1",
doi = "10.1093/cvr/cvn141",
language = "English (US)",
volume = "79",
pages = "715--721",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
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TY - JOUR

T1 - Blunted excitability of aortic baroreceptor neurons in diabetic rats

T2 - Involvement of hyperpolarization-activated channel

AU - Li, Yulong

AU - Tran, Thai Paul

AU - Muelleman, Robert Leo

AU - Schultz, Harold D

PY - 2008/9/1

Y1 - 2008/9/1

N2 - 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.

AB - 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.

KW - Autonomic nervous system

KW - Baroreflex

KW - Diabetes

KW - Electrophysiology

KW - Ion channels

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U2 - 10.1093/cvr/cvn141

DO - 10.1093/cvr/cvn141

M3 - Article

C2 - 18524809

AN - SCOPUS:52449117177

VL - 79

SP - 715

EP - 721

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 4

ER -