Modulating Properties of Hyperpolarization-Activated Cation Current in Urinary Bladder Smooth Muscle Excitability: A Simulation Study

Mahapatra, Chitaranjan; Manchanda, Rohit

doi:10.1007/978-981-10-8639-7_27

Cited by 4 publications

(8 citation statements)

References 15 publications

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“…Moreover, they offer a platform for hypothesis testing and guide experimental design, ultimately accelerating the discovery of novel targets and therapies for various physiological and pathological conditions. While numerous computational models have been published regarding DSM cell electrophysiology, none of them have incorporated the TRPM4 channel for investigation [82][83][84]86,87]. Computational modeling is an ongoing process, wherein established models are continuously refined with new experimental findings to yield more fruitful research outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…The complexity of these models has steadily increased over the years as more experimental data has become available. Several DSM cell electrophysiology models have been mathematically designed to mimic the behavior of DSM electrical activities [82][83][84]86,87]. These models also serve as a bridge between cellular-level models and tissue-level function, offering a comprehensive understanding of DSM cell electrical activity across different scales.…”

Section: Model Adaptationmentioning

confidence: 99%

“…While computational models for various types of smooth muscle cells, such as intestinal [63], uterine [64][65][66], ureter [67][68][69], jejunal [70], vas deferens [71][72][73][74], gastric [75,76], mesenteric [77], small bowel [78], urethra [79,80], and arterial [81] smooth muscle cells, have been developed, models for DSM cells are relatively underdeveloped. The models published on DSM electrophysiology have yet to explore the modulatory properties of TRPM4 ion channels in DSP action potentials [82][83][84][85][86][87][88]. The present in silico model aims to elucidate the biophysical mechanisms underlying the DSM electrophysiology, aiming to investigate the impact of the TRPM4 ion channel on the firing rate of DSM action potentials.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity

Mahapatra,

Thakkar

2024

Preprint

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Enhanced electrical activity in detrusor smooth muscle (DSM) cells is a key factor in detrusor overactivity which causes overactive bladder pathological disorders. Transient receptor potential melastatin-4 (TRPM4) channels, calcium-activated cation channels, play a role in regulating DSM electrical activities. These channels likely contribute to depolarizing the DSM cell membrane, leading to bladder overactivity. Our research focuses on understanding TRPM4 channel function in mouse DSM cells using computational modeling. We aimed to create a detailed computational model of the TRPM4 channel based on existing electrophysiological data. We employed a modified Hodgkin-Huxley model with an incorporated TRP-like current to simulate action potential firing in response to current and synaptic stimulus inputs. Validation against experimental data showed close agreement with our simulations. Our model is the first to analyze the TRPM4 channel's role in DSM electrical activity, potentially revealing insights into bladder overactivity. In conclusion, TRPM4 channels are pivotal in regulating human DSM function and TRPM4 channel inhibitors could be promising targets for treating overactive bladder.

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Section: Discussionmentioning

confidence: 99%

Section: Model Adaptationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity

Mahapatra,

Thakkar

2024

Preprint

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“…According to several reports, the lower urinary tract, which includes VSM, consists of a set of ion channels, such as the voltage-gated Ca 2+ channel (T and L type), the voltage-gated K + channel (Kir, Kv1, Kdr), the voltage-gated Na + channel, voltage-gated Cl − channel Ca 2+ -activated K + (KCa) channels (large conductance and small conductance), the K ATP channel, the CRAC channel, the TRPM channel, and leak channels [ 81 , 82 , 83 ]. The K ATP , Kir, KA, and Kdr are ATP-gated, inward rectifying, A-type, and delayed rectifier-type voltage-gated K + channels.…”

Section: Ion Channel Biophysics In Smooth Musclementioning

confidence: 99%

Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: The Role of the Membrane Potential and Ion Channels

Mahapatra,

Kumar

2024

Pathophysiology

Self Cite

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The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions, such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.

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“…The channels in this process are called calcium release-activated channels (CRAC) in various smooth muscles [68]. According to several reports, the lower urinary tract which includes VSM consists of a set of ion channels, such as voltage-gated Ca 2+ channel (T and L type), voltage-gated K + channel (Kir, KATP, Kv1, Kdr), voltage-gated Na + channel, voltage-gated Clchannel Ca 2+ -activated K+ (KCa) channels (large conductance and small conductance) CRAC channel, TRPM channel, and leak channels [69][70][71]. The Kir, KATP, KA, and Kdr are inward rectifying, ATP-gated, A-type, and delayed rectifiertype voltage-gated K + channels.…”

Section: Ion Channel Biophysics In Smooth Musclementioning

confidence: 99%

Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: Role of the Membrane Potential and Ion Channels

Mahapatra,

Kumar

2024

Preprint

View full text Add to dashboard Cite

The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.

show abstract

Modulating Properties of Hyperpolarization-Activated Cation Current in Urinary Bladder Smooth Muscle Excitability: A Simulation Study

Cited by 4 publications

References 15 publications

In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity

In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity

Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: The Role of the Membrane Potential and Ion Channels

Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: Role of the Membrane Potential and Ion Channels

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