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

Abstract

4Bladder cystopathy is a common urological complication of diabetes, and has been associated 3 5 with changes in parasympathetic ganglionic transmission and some measures of neuronal excitability in 3 6 male mice. To determine whether type II diabetes also impacts excitability of parasympathetic ganglionic 3 7 neurons in females, we investigated neuronal excitability and firing properties, as well as underlying ion 3 8 channel expression, in major pelvic ganglion (MPG) neurons in control, 10-week, and 21-week db/db 3 9mice. Type II diabetes in Lepr db/db animals caused a non-linear change in excitability and firing properties 4 0 of MPG neurons. At 10 weeks, cells exhibited increased excitability as demonstrated by an increased 4 1 likelihood of firing multiple spikes upon depolarization, decreased rebound spike latency, and overall 4 2 narrower action potential half-widths as a result of increased depolarization and repolarization slopes. 4 3Conversely, at 21 weeks MPG neurons of db/db mice reversed these changes, with spiking patterns and 4 4 action-potential properties largely returning to control levels. These changes are associated with 4 5 numerous time-specific changes in calcium, sodium, and potassium channel subunit mRNA levels. 4 6However, Principal Components Analysis of channel expression patterns revealed that the rectification of 4 7 excitability is not simply a return to control levels, but rather a distinct ion channel expression profile in 4 8