Properties of SK3 channel-expressing PDGFRα (+) cells in the rodent urinary bladder

Hayashi, Tokumasa; Hashitani, Hikaru; Takeya, Mitsue; Uemura, Keiichiro; Nakamura, Kei‐ichiro; Igawa, Tsukasa

doi:10.1016/j.ejphar.2019.172552

Cited by 9 publications

(14 citation statements)

References 38 publications

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“…Thus, the property of SK3 (−) PDGFRα (+) cells, in terms of intercellular coupling, is similar to that of SK3 (+) PDGFRα (+) cells in DSM layer that appear not to communicate with themselves nor DSM cells. 7 The lack of intercellular communications between SK3 (−) PDGFRα (+) cells is apparently inconsistent with the previous finding in the rat bladder. 16 Thus, Ca 2+ and membrane potential waves evoked in the suburothelial regions of the rat bladder propagate not only horizontally but also transversally towards the DSM layer, although the contribution of PDGFRα (+) cells to signal transmissions were not examined.…”

Section: Discussioncontrasting

confidence: 66%

“…It was also envisaged that PDGFRα (+) cells play an important role in purinergic inhibitory regulation of DSM as they vigorously respond to P2Y1-stimulation developing SK-dependent outward currents or hyperpolarisations. 6 However, Ca 2+ imaging in DSM tissue preparations in situ failed to demonstrate any inhibition of spontaneous DSM Ca 2+ transients during P2Y 1 purinoceptor-mediated rises in Ca 2+ levels in PDGFRα (+) cells, 7 indicating a lack of communication between PDGFRα (+) cells and DSM cells. Therefore, bladder PDGFRα (+) cells may have roles other than stabilizing DSM excitability.…”

Section: Introductionmentioning

confidence: 94%

“…Preparations of the bladder lamina propria, proximal renal pelvis or seminal vesicle mucosa loaded with 1 μM Calbrite590 AM, a fluorescent Ca 2+ indicator (special packaging, Dojindo, Japan) were superfused with dyefree, warmed (36°C) physiological salt solution (PSS) at a constant flow rate (about 2 mL/min), illuminated at 575 nm and fluorescence emissions above 590 nm were detected as described previously. 7 Relative amplitude of Ca 2+ transients was expressed as the ratio (F t/ F 0 ) of the fluorescence generated by an event (F t ) against baseline (F 0 ).…”

Section: Fluorescence Intracellular Ca 2+ Imagingmentioning

confidence: 99%

“…In contrast, PDGFRα (+) cells with stellate or elongated cell bodies within the DSM layer were SK3-immmunoreactive ( Figure 1C,D, N = 6), verifying antibody specificity previously used in the guinea-pig bladder. 7 3.2 | Ca 2+ signaling in PDGFRα (+) cells of the bladder lamina propria…”

Section: Distribution and Sk3 Immunoreactivity In Pdgfrα (+) Cells mentioning

confidence: 99%

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Functional heterogeneity of PDGFRα (+) cells in spontaneously active urogenital tissues

Hashitani

Mitsui

Lang

2020

Neurourology and Urodynamics

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Aims As PDGFRα (+) cells appear not to suppress the excitability of detrusor smooth muscle by generating SK3‐dependent hyperpolarising as proposed in the gastrointestinal tract, we further explored the functional roles of PDGFRα (+) cells in regulating the spontaneous activity of urogenital tissues. Methods Using PDGFRα‐eGFP mice, intracellular Ca2+ signaling in PDGFRα (+) cells of the bladder lamina propria, renal pelvis, and seminal vesicle were visualized using Cal‐590 fluorescence. The distribution and SK3 expression of PDGFRα (+) cells were also examined by immunohistochemistry. Results In the bladder lamina propria, SK3 (−) PDGFRα (+) cells exhibited spontaneous Ca2+ transients and responded to stimulation of P2Y1 purinoceptors with MRS2365 (100 nM) or adenosine diphosphate (ADP) (100 μM) by developing Ca2+ transients. In the proximal renal pelvis, PDGFRα (+) cells were distributed in the mucosal, muscular and serosal layers but did not express SK3 immunoreactivity. PDGFRα (+) cells in the musculature resembling atypical smooth muscle cells generated spontaneous Ca2+ transients that were partially suppressed upon P2Y1‐stimulation, while vigorously responding to human angiotensin II (100 nM). In the seminal vesicle, PDGFRα (+) cells in the musculature but not mucosa expressed SK3 immunoreactivity. In the mucosa, the P2Y1 stimulation evoked Ca2+ transients in both PDGFRα (+) cells and PDGFRα (−) cells. Conclusion PDGFRα (+) cells in spontaneously active urogenital tissues display heterogeneity in terms of their SK3 expression and P2Y1‐induced Ca2+ responses. Muscular PDGFRα (+) cells in the renal pelvis and mucosal PDGFRα (+) cells in the seminal vesicle may generate depolarizing signals to drive smooth muscle cells.

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Section: Discussioncontrasting

confidence: 66%

Section: Introductionmentioning

confidence: 94%

Section: Fluorescence Intracellular Ca 2+ Imagingmentioning

confidence: 99%

Section: Distribution and Sk3 Immunoreactivity In Pdgfrα (+) Cells mentioning

confidence: 99%

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Functional heterogeneity of PDGFRα (+) cells in spontaneously active urogenital tissues

Hashitani

Mitsui

Lang

2020

Neurourology and Urodynamics

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“…In the mouse bladder, stimulation of P2Y 1 receptors induces Ca 2+ transients in PDGFRα + interstitial cells, which did not suppress the LVDCC‐dependent spontaneous Ca 2+ transients in the neighbouring detrusor SMCs (Hayashi et al . 2019; Hashitani et al . 2020).…”

Section: Discussionmentioning

confidence: 99%

PDGFRα⁺ subepithelial interstitial cells act as a pacemaker to drive smooth muscle of the guinea pig seminal vesicle

Takeya

Higashi

Hashitani

et al. 2022

The Journal of Physiology

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Smooth muscle cells (SMCs) of the guinea pig seminal vesicle (SV) develop spontaneous phasic contractions, Ca2+ flashes and electrical slow waves in a mucosa‐dependent manner, and thus it was envisaged that pacemaker cells reside in the mucosa. Here, we aimed to identify the pacemaker cells in SV mucosa using intracellular microelectrode and fluorescence Ca2+ imaging techniques. Morphological characteristics of the mucosal pacemaker cells were also investigated using focused ion beam/scanning electron microscopy tomography and fluorescence immunohistochemistry. Two populations of mucosal cells developed spontaneous Ca2+ transients and electrical activity, namely basal epithelial cells (BECs) and subepithelial interstitial cells (SICs). Pancytokeratin‐immunoreactive BECs were located on the apical side of the basement membrane (BM) and generated asynchronous, irregular spontaneous Ca2+ transients and spontaneous transient depolarisations (STDs). The spontaneous Ca2+ transients and STDs were not diminished by 10 μM nifedipine but abolished by 10 μM cyclopiazonic acid (CPA). Platelet‐derived growth factor receptor α (PDGFRα)‐immunoreactive SICs were distributed just beneath the basal side of the BM and developed synchronous Ca2+ oscillations and electrical slow waves, which were suppressed by 3 μM nifedipine and abolished by 10 μM CPA. In SV mucosal preparations in which some smooth muscle bundles remained attached, SICs and residual SMCs developed temporally correlated spontaneous Ca2+ transients. Neurobiotin injected into SICs spread not only to neighbouring SICs but also to neighbouring SMCs or vice versa. These results suggest that PDGFRα+ SICs electrotonically drive the spontaneous contractions of SV smooth muscle. Key points In many visceral smooth muscle organs, spontaneous contractions are electrically driven by non‐muscular pacemaker cells. In guinea pig seminal vesicles (SVs), as yet unidentified mucosal cells appear to drive neighbouring smooth muscle cells (SMCs). Two populations of spontaneously active cells are distributed in the SV mucosa. Basal epithelial cells (BECs) generate asynchronous, irregular spontaneous Ca2+ transients and spontaneous transient depolarisations (STDs). In contrast, subepithelial interstitial cells (SICs) develop synchronous Ca2+ oscillations and electrical slow waves. Pancytokeratin‐immunoreactive (IR) BECs are located on the apical side of the basement membrane (BM), while platelet‐derived growth factor receptor α (PDGFRα)‐IR SICs are located on the basal side of the BM. Spontaneous Ca2+ transients in SICs are synchronised with those in SV SMCs. Dye‐coupling between SICs and SMCs suggests that SICs act as pacemaker cells to drive the spontaneous contractions of SV smooth muscle.

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Should we be revisiting LUT basic science and clinical measurement of LUT sensation to improve patient care? ICI‐RS 2019

McCloskey

Wyndaele

Speich

et al. 2020

Neurourology and Urodynamics

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Aims This article reviews current knowledge of the underpinning mechanisms of how the bladder senses fullness locally and also revisits clinical measurements of lower urinary tract sensation. The former represents cellular sensing during bladder filling whereas the latter describes the sensations leading to conscious perception of bladder fullness. Methods The topic was discussed in a “think tank” session at the 2019 International Consultation on Incontinence—Research Symposium in Bristol, UK; summarized in the present review. Results Recent advances in the basic science of bladder sensing relating to (a) the bladder wall—urothelial cells, sensory nerves, interstitial cells, and smooth muscle cells and (b) putative chemo/mechanosensors in the urethra—paraneurons or “brush cells” are discussed. Validated clinical measurement of lower urinary tract sensation is reviewed in the context of how this could be better harnessed for patient benefit. We discuss the potential of app/tablet/mobile technology based on triggers and distractors to override aberrant local sensing/higher sensation and how these technologies could be utilized in treatment. Conclusions We conclude that a better understanding of bladder sensation is essential to inform clinical management of lower urinary tract symptoms.

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Properties of SK3 channel-expressing PDGFRα (+) cells in the rodent urinary bladder

Cited by 9 publications

References 38 publications

Functional heterogeneity of PDGFRα (+) cells in spontaneously active urogenital tissues

Functional heterogeneity of PDGFRα (+) cells in spontaneously active urogenital tissues

PDGFRα⁺ subepithelial interstitial cells act as a pacemaker to drive smooth muscle of the guinea pig seminal vesicle

Should we be revisiting LUT basic science and clinical measurement of LUT sensation to improve patient care? ICI‐RS 2019

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Properties of SK3 channel-expressing PDGFRα (+) cells in the rodent urinary bladder

Cited by 9 publications

References 38 publications

Functional heterogeneity of PDGFRα (+) cells in spontaneously active urogenital tissues

Functional heterogeneity of PDGFRα (+) cells in spontaneously active urogenital tissues

PDGFRα+ subepithelial interstitial cells act as a pacemaker to drive smooth muscle of the guinea pig seminal vesicle

Should we be revisiting LUT basic science and clinical measurement of LUT sensation to improve patient care? ICI‐RS 2019

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PDGFRα⁺ subepithelial interstitial cells act as a pacemaker to drive smooth muscle of the guinea pig seminal vesicle