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Quantitative Sudies of Spontaneous Electrical Activities in Detrusor Smooth Muscle Cells towards Understanding Urinary Bladder Overactivities
Author(s) -
Mahapatra Chitaranjan,
Manchanda Rohit
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03360
Subject(s) - depolarization , hyperpolarization (physics) , membrane potential , chemistry , purinergic receptor , biophysics , neuroscience , neurotransmitter , bk channel , excitatory postsynaptic potential , efferent , electrophysiology , biology , adenosine , central nervous system , inhibitory postsynaptic potential , afferent , biochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
Context The urinary incontinence (UI) is defined as the involuntary loss of urine and associated with the enhanced spontaneous contractions of the detrusor smooth muscle (DSM). The spontaneously evoked action potentials (sAPs) in DSM cells initiate and modulate these contractions. The DSM is strongly innervated, connecting approximately 16000 afferent and efferent axons from ganglion neurons. It generates sAPs due to the stochastic nature of purinergic neurotransmitter release from the parasympathetic nerve. Objectives The aim of this current study is to understand the putative relationship between the fluctuating ion channel conductances and stochastically release of ATP in generating sAPs. Methods The neurotransmitter current was considered as an independent excitatory conductance in the model where g ex (t) and E ex are the one‐variable stochastic process conductance and the reversal potential respectively. In addition, D ex and λ 1 (t) are known as the diffusion coefficients and Gaussian white noise. The point‐conductance is incorporated into a single DSM cell model based on single cylindrical compartment. Results The elicited AP consists an after depolarization and after hyperpolarization phase. The AP peak amplitude and duration are about 15 mV and 40 ms respectively. The stochastic nature of purinergic neurotransmitter is designed by a point process model. Then, the random injection of point process model is conducted to elicit a series of sAPs and membrane depolarization for 5 seconds. The membrane resting potential is held at − 50 mV with a 3 mV of fluctuation. The stochastically depolarization up to 20 mV activates the T‐type Ca 2+ channel first and then the L‐type Ca 2+ channel to generate action potential. The Figure 1 A illustrates series of AP generation in the DSM cell due to stochastically depolarizations. The model does not evoke any AP and depolarization, when the conductance of T‐type Ca 2+ channel is set to zero (Figure 1 B). Conclusions From the results, it is found that the T‐type Ca 2+ channel blocker can be used as a new pharmacological target for the UI. In addition, an extended multidimensional models will a provide windows of insight into the factors that govern excitability and contraction in both normal and unstable bladder. Support or Funding Information This work is supported in part by Department of Biotechnology (DBT), India (grant number BT/PR12973/MED/122/47/2016).Effects of T‐type Ca2+ channel blockers on AP generation.