Alterations of calcium channels and cell excitability in intracardiac ganglion neurons from type 2 diabetic rats

Jinxu Liu, Huiyin Tu, Hong Zheng, Libin Zhang, Thai P. Tran, Robert Leo Muelleman, Yulong Li

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Clinical study has demonstrated that patients with type 2 diabetes with attenuated arterial baroreflex have higher mortality rate compared with those without arterial baroreflex dysfunction. As a final pathway for the neural control of the cardiac function, functional changes of intracardiac ganglion (ICG) neurons might be involved in the attenuated arterial baroreflex in the type 2 diabetes mellitus (T2DM). Therefore, we measured the ICG neuron excitability and Ca 2+ channels in the sham and T2DM rats. T2DM was induced by a combination of both high-fat diet and low-dose streptozotocin (STZ, 30 mg/kg ip) injection. After 12-14 wk of the above treatment, the T2DM rats presented hyperglycemia, hyperlipidemia, and insulin resistance but no hyperinsulin- emia, which closely mimicked the clinical features of the patients with T2DM. Data from immunofluorescence staining showed that L, N, P/Q, and R types of Ca 2+ channels were expressed in the ICG neurons, but only protein expression of N-type Ca 2+ channels was decreased in the ICG neurons from T2DM rats. Using whole cell patch-clamp technique, we found that T2DM significantly reduced the Ca 2+ currents and cell excitability in the ICG neurons. w-Conotoxin GVIA (a specific N-type Ca 2+ channel blocker, 1 ^M) lowered the Ca 2+ currents and cell excitability toward the same level in sham and T2DM rats. These results indicate that the decreased N-type Ca 2+ channels contribute to the suppressed ICG neuron excitability in T2DM rats. From this study, we think high-fat diet/STZ injection- induced T2DM might be an appropriate animal model to test the cellular and molecular mechanisms of cardiovascular autonomic dysfunction.

Original languageEnglish (US)
Pages (from-to)C1119-C1127
JournalAmerican Journal of Physiology - Cell Physiology
Volume302
Issue number8
DOIs
StatePublished - Apr 15 2012

Fingerprint

Calcium Channels
Ganglia
Type 2 Diabetes Mellitus
Neurons
Baroreflex
High Fat Diet
Conotoxins
Neural Pathways
Injections
Hyperinsulinism
Patch-Clamp Techniques
Streptozocin
Hyperlipidemias
Hyperglycemia
Fluorescent Antibody Technique
Insulin Resistance
Animal Models
Staining and Labeling
Mortality

Keywords

  • Action potential
  • Intracardiac ganglia
  • Rat
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Alterations of calcium channels and cell excitability in intracardiac ganglion neurons from type 2 diabetic rats. / Liu, Jinxu; Tu, Huiyin; Zheng, Hong; Zhang, Libin; Tran, Thai P.; Muelleman, Robert Leo; Li, Yulong.

In: American Journal of Physiology - Cell Physiology, Vol. 302, No. 8, 15.04.2012, p. C1119-C1127.

Research output: Contribution to journalArticle

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abstract = "Clinical study has demonstrated that patients with type 2 diabetes with attenuated arterial baroreflex have higher mortality rate compared with those without arterial baroreflex dysfunction. As a final pathway for the neural control of the cardiac function, functional changes of intracardiac ganglion (ICG) neurons might be involved in the attenuated arterial baroreflex in the type 2 diabetes mellitus (T2DM). Therefore, we measured the ICG neuron excitability and Ca 2+ channels in the sham and T2DM rats. T2DM was induced by a combination of both high-fat diet and low-dose streptozotocin (STZ, 30 mg/kg ip) injection. After 12-14 wk of the above treatment, the T2DM rats presented hyperglycemia, hyperlipidemia, and insulin resistance but no hyperinsulin- emia, which closely mimicked the clinical features of the patients with T2DM. Data from immunofluorescence staining showed that L, N, P/Q, and R types of Ca 2+ channels were expressed in the ICG neurons, but only protein expression of N-type Ca 2+ channels was decreased in the ICG neurons from T2DM rats. Using whole cell patch-clamp technique, we found that T2DM significantly reduced the Ca 2+ currents and cell excitability in the ICG neurons. w-Conotoxin GVIA (a specific N-type Ca 2+ channel blocker, 1 ^M) lowered the Ca 2+ currents and cell excitability toward the same level in sham and T2DM rats. These results indicate that the decreased N-type Ca 2+ channels contribute to the suppressed ICG neuron excitability in T2DM rats. From this study, we think high-fat diet/STZ injection- induced T2DM might be an appropriate animal model to test the cellular and molecular mechanisms of cardiovascular autonomic dysfunction.",
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AU - Muelleman, Robert Leo

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