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

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.