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

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.