ArticlePLoS computational biology2018
A biophysically detailed computational model of urinary bladder small DRG neuron soma.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 28 citations in OpenAlex.
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- Computational modeling to study the impact of changes in Nav1.8 sodium channel on neuropathic pain.Frontiers in computational neuroscience · 2024Article
- Kinetics and functional consequences of BK channels activation by N-type CaFrontiers in cellular neuroscience · 2024Article
- How Merkel cells transduce mechanical stimuli: A biophysical model of Merkel cells.PLoS computational biology · 2023Article
- Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.Advanced genetics (Hoboken, N.J.) · 2023Article
- Predictive analytics identifies key factors driving hyperalgesic priming of muscle sensory neurons.Frontiers in neuroscience · 2023Article
- Identification of key factors driving inflammation-induced sensitization of muscle sensory neurons.Frontiers in neuroscience · 2023Article
- Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Computational modelling of nerve stimulation and recording with peripheral visceral neural interfaces.Journal of neural engineering · 2021Article
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- DecipheringFrontiers in cellular neuroscience · 2021Article
- Features of Action Potentials from Identified Thalamic Nuclei in Anesthetized Patients.Brain sciences · 2020Article
- Computational analysis of a 9D model for a small DRG neuron.Journal of computational neuroscience · 2020Article
- Modeling a Nociceptive Neuro-Immune Synapse Activated by ATP and 5-HT in Meninges: Novel Clues on Transduction of Chemical Signals Into Persistent or Rhythmic Neuronal Firing.Frontiers in cellular neuroscience · 2020Article
- Examining Sodium and Potassium Channel Conductances Involved in Hyperexcitability of Chemotherapy-Induced Peripheral Neuropathy: A Mathematical and Cell Culture-Based Study.Frontiers in computational neuroscience · 2020Article
- A computational model of large conductance voltage and calcium activated potassium channels: implications for calcium dynamics and electrophysiology in detrusor smooth muscle cells.Journal of computational neuroscience · 2019Article
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
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 reduces action potential (AP) firing frequency. We also show that SKCa is more potent in reducing AP spiking than the large-conductance KCa channel (BKCa) in these neurons. Moreover, BKCa was found to contribute to the fast AHP (fAHP) and SKCa to the medium-duration (mAHP) and slow AHP (sAHP). We also report that the slow inactivating A-type K+ channel (slow KA) current in these neurons is composed of 2 components: an initial fast inactivating (time constant ∼ 25-100 ms) and a slow inactivating (time constant ∼ 200-800 ms) current. We discuss the implications of our findings, and how our detailed model can help further our understanding of the role of C-fibre afferents in the physiology of urinary bladder as well as in certain disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.