Computational Studies on Bladder Smooth Muscle: Modeling Ion Channels and their Role in Generating Electrical Activity

Mahapatra, Chitaranjan; Manchanda, Rohit

doi:10.1016/j.bpj.2014.11.3204

Cited by 7 publications

(6 citation statements)

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“…One of the first comprehensive smooth muscle spike models was reported in 2011 for uterine smooth muscle cells. 61 Among the vas deferens and urinary bladder smooth muscle, a model for the spike of the vas deferens has not yet been reported except in a nascent form, 62,63 while for DSM progress has been more substantial.…”

Section: Recent Developmentsmentioning

confidence: 99%

Electrophysiology of Syncytial Smooth Muscle

2019

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As in other excitable tissues, two classes of electrical signals are of fundamental importance to the functioning of smooth muscles: junction potentials, which arise from neurotransmission and represent the initiation of excitation (or in some instances inhibition) of the tissue, and spikes or action potentials, which represent the accomplishment of excitation and lead on to contractile activity. Unlike the case in skeletal muscle and in neurons, junction potentials and spikes in smooth muscle have been poorly understood in relation to the electrical properties of the tissue and in terms of their spatiotemporal spread within it. This owes principally to the experimental difficulties involved in making precise electrical recordings from smooth muscles and also to two inherent features of this class of muscle, ie, the syncytial organization of its cells and the distributed innervation they receive, which renders their biophysical analysis problematic. In this review, we outline the development of hypotheses and knowledge on junction potentials and spikes in syncytial smooth muscle, showing how our concepts have frequently undergone radical changes and how recent developments hold promise in unraveling some of the many puzzles that remain. We focus especially on computational models and signal analysis approaches. We take as illustrative examples the smooth muscles of two organs with distinct functional characteristics, the vas deferens and urinary bladder, while also touching on features of electrical functioning in the smooth muscles of other organs.

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Section: Recent Developmentsmentioning

confidence: 99%

Electrophysiology of Syncytial Smooth Muscle

2019

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“…Our validated model was then employed in order to resolve existing conflicts, and to gain new biological insights that are experimentally testable (See Discussion ). Some preliminary results of this investigation have previously been communicated in brief [ 43 , 44 , 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle

2018

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Urinary incontinence is associated with enhanced spontaneous phasic contractions of the detrusor smooth muscle (DSM). Although a complete understanding of the etiology of these spontaneous contractions is not yet established, it is suggested that the spontaneously evoked action potentials (sAPs) in DSM cells initiate and modulate the contractions. In order to further our understanding of the ionic mechanisms underlying sAP generation, we present here a biophysically detailed computational model of a single DSM cell. First, we constructed mathematical models for nine ion channels found in DSM cells based on published experimental data: two voltage gated Ca2+ ion channels, an hyperpolarization-activated ion channel, two voltage-gated K+ ion channels, three Ca2+-activated K+ ion channels and a non-specific background leak ion channel. The ion channels’ kinetics were characterized in terms of maximal conductances and differential equations based on voltage or calcium-dependent activation and inactivation. All ion channel models were validated by comparing the simulated currents and current-voltage relations with those reported in experimental work. Incorporating these channels, our DSM model is capable of reproducing experimentally recorded spike-type sAPs of varying configurations, ranging from sAPs displaying after-hyperpolarizations to sAPs displaying after-depolarizations. The contributions of the principal ion channels to spike generation and configuration were also investigated as a means of mimicking the effects of selected pharmacological agents on DSM cell excitability. Additionally, the features of propagation of an AP along a length of electrically continuous smooth muscle tissue were investigated. To date, a biophysically detailed computational model does not exist for DSM cells. Our model, constrained heavily by physiological data, provides a powerful tool to investigate the ionic mechanisms underlying the genesis of DSM electrical activity, which can further shed light on certain aspects of urinary bladder function and dysfunction.

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“…APs in smooth muscle cells are characterized by slower kinetics than skeletal muscle, with durations nearly fifty times longer [2]. APs are generated in the urinary bladder [18,32], vas deferens [33,34], urethra [35,36], and ureter [37,38] smooth muscles. Slow waves, rhythmic electrophysiological events in the gastrointestinal (GI) tract, are generated and propagated by interstitial cells of Cajal (ICC), which are electrically coupled to smooth muscle cells [39].…”

Section: Membrane Potential In Smooth Muscle Contractionmentioning

confidence: 99%

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

Mahapatra,

Kumar

2024

Preprint

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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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Computational Studies on Bladder Smooth Muscle: Modeling Ion Channels and their Role in Generating Electrical Activity

Cited by 7 publications

References 0 publications

Electrophysiology of Syncytial Smooth Muscle

Electrophysiology of Syncytial Smooth Muscle

A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle

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

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