Changes in excitability and ion channel expression in neurons of the major pelvic ganglion in female type II diabetic mice

Michael Gray, Kawasi M. Lett, V. B. Garcia, Cindy W. Kyi, K. Pennington, L. Schulz, D. Schulz
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引用次数: 4

Abstract

Bladder cystopathy is a common urological complication of diabetes, and has been associated with changes in parasympathetic ganglionic transmission and some measures of neuronal excitability in male mice. To determine whether type II diabetes also impacts excitability of parasympathetic 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 db/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 db/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 the rectification of excitability is not simply a return to control levels, but rather a distinct ion channel expression profile in 21-week db/db neurons. These data indicate that type II diabetes can impact the excitability of post-ganglionic, parasympathetic bladder-innervating 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 db/db MPG neurons.
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雌性II型糖尿病小鼠盆腔神经节神经元兴奋性和离子通道表达的变化
膀胱囊肿病是糖尿病常见的泌尿系统并发症,与雄性小鼠副交感神经节传递和某些神经元兴奋性的改变有关。为了确定II型糖尿病是否也会影响女性副交感神经节神经元的兴奋性,我们研究了对照、10周和21周db/db小鼠的主要盆腔神经节(MPG)神经元的兴奋性和放电特性,以及潜在的离子通道表达。II型糖尿病在Leprdb/db动物中引起MPG神经元兴奋性和放电特性的非线性变化。在第10周时,细胞表现出增强的兴奋性,表现为在去极化时发射多个尖峰的可能性增加,反弹尖峰潜伏期减少,由于去极化和复极化斜率增加,动作电位半宽总体变窄。相反,在21周时,db/db小鼠的MPG神经元逆转了这些变化,其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显示,兴奋性的纠正不仅仅是回到控制水平,而是21周db/db神经元中不同的离子通道表达谱。这些数据表明,II型糖尿病可以影响雌性小鼠神经节后、副交感膀胱神经支配神经元的兴奋性,并提示糖尿病患者这些特性的非线性进展可能是通道表达代偿性变化的结果,通道表达可纠正db/db MPG神经元的放电模式中断。
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