Bladder cystopathy and autonomic dysfunction are common complications of diabetes, and have been associated with changes in ganglionic transmission and some measures of neuronal excitability in male mice. To determine whether type II diabetes also impacts excitability of ganglionic neurons in females, we investigated neuronal excitability and firing properties, as well as underlying ion channel expression, in major pelvic ganglion (MPG) neurons in control, 10-week, and 21-week Leprdb/db mice. Type II diabetes in Leprdb/db animals caused a non-linear change in excitability and firing properties of MPG neurons. At 10 weeks, cells exhibited increased excitability as demonstrated by an increased likelihood of firing multiple spikes upon depolarization, decreased rebound spike latency, and overall narrower action potential half-widths as a result of increased depolarization and repolarization slopes. Conversely, at 21 weeks MPG neurons of Leprdb/db mice reversed these changes, with spiking patterns and action-potential properties largely returning to control levels. These changes are associated with numerous time-specific changes in calcium, sodium, and potassium channel subunit mRNA levels. However, Principal Components Analysis of channel expression patterns revealed that rectification of excitability is not simply a return to control levels, but rather a distinct ion channel expression profile in 21-week Leprdb/db neurons. These data indicate that type II diabetes can impact the excitability of post-ganglionic, autonomic neurons of female mice, and suggest that the non-linear progression of these properties with diabetes may be the result of compensatory changes in channel expression that act to rectify disrupted firing patterns of Leprdb/db MPG neurons.

中文翻译：

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雌性II型糖尿病小鼠盆腔主要神经节神经元兴奋性和离子通道表达的变化

膀胱膀胱病变和自主神经功能障碍是糖尿病的常见并发症，并且与神经节传递的变化和雄性小鼠神经元兴奋性的一些测量有关。为了确定 II 型糖尿病是否也影响女性神经节神经元的兴奋性，我们研究了对照、10 周和 21 周的主要骨盆神经节 (MPG) 神经元的神经元兴奋性和放电特性，以及潜在的离子通道表达Leprdb/db 小鼠。Leprdb/db 动物的 II 型糖尿病导致 MPG 神经元的兴奋性和放电特性发生非线性变化。在第 10 周时，细胞表现出更高的兴奋性，如去极化时激发多个尖峰的可能性增加、回弹尖峰潜伏期减少、由于去极化和复极化斜率增加，整体动作电位半峰宽变窄。相反，在 21 周时 Leprdb/db 小鼠的 MPG 神经元逆转了这些变化，尖峰模式和动作电位特性在很大程度上恢复到控制水平。这些变化与钙、钠和钾通道亚基 mRNA 水平的许多时间特异性变化有关。然而，通道表达模式的主成分分析表明，兴奋性的矫正不仅仅是恢复到控制水平，而是 21 周 Leprdb/db 神经元中独特的离子通道表达谱。这些数据表明，II 型糖尿病会影响雌性小鼠神经节后自主神经元的兴奋性，