A biophysically detailed computational model of urinary bladder small DRG neuron soma

PLoS Computational Biology
Darshan Mandge, Rohit Manchanda

Abstract

Bladder small DRG neurons, which are putative nociceptors pivotal to urinary bladder function, express more than a dozen different ionic membrane mechanisms: ion channels, pumps and exchangers. Small-conductance Ca2+-activated K+ (SKCa) channels which were earlier thought to be gated solely by intracellular Ca2+ concentration ([Ca]i) have recently been shown to exhibit inward rectification with respect to membrane potential. The effect of SKCa inward rectification on the excitability of these neurons is unknown. Furthermore, studies on the role of KCa channels in repetitive firing and their contributions to different types of afterhyperpolarization (AHP) in these neurons are lacking. In order to study these phenomena, we first constructed and validated a biophysically detailed single compartment model of bladder small DRG neuron soma constrained by physiological data. The model includes twenty-two major known membrane mechanisms along with intracellular Ca2+ dynamics comprising Ca2+ diffusion, cytoplasmic buffering, and endoplasmic reticulum (ER) and mitochondrial mechanisms. Using modelling studies, we show that inward rectification of SKCa is an important parameter regulating neuronal repetitive firing and that its absence re...Continue Reading

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Citations

Aug 31, 2020·Journal of Computational Neuroscience·Parul VermaDoraiswami Ramkrishna
Dec 23, 2020·Brain Sciences·Jesús Pastor, Lorena Vega-Zelaya
Sep 28, 2021·Frontiers in Neuroscience·Sridevi NagarajaJaques Reifman
Nov 6, 2021·Journal of Neural Engineering·Calvin D EiberJames B Fallon

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Software Mentioned

NEURON simulator
OriginPro
NEURON
MATLAB
webPlotDigitizer
mtPericam

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