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Mechanosensory corpuscles detect transient touch and vibration in the skin of vertebrates, enabling precise sensation of the physical environment. The corpuscle contains a mechanoreceptor afferent surrounded by lamellar cells (LCs), but corpuscular ultrastructure and the role of LCs in touch detection are unknown. We report the three-dimensional architecture of the avian Meissner (Grandry) corpuscle acquired using enhanced focused ion beam scanning electron microscopy and machine learning-based segmentation. The corpuscle comprises a stack of LCs interdigitated with terminal endings from two afferents. Simultaneous electrophysiological recordings from both cell types revealed that mechanosensitive LCs use calcium influx to trigger action potentials in the afferent and thus serve as physiological touch sensors in the skin. The elaborate architecture and bicellular sensory mechanism in the corpuscles, which comprises the afferents and LCs, create the capacity for nuanced encoding of the submodalities of touch.
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This content will become publicly available on September 1, 2026
Pharmacological Targeting of Hyperpolarization‐Activated Cyclic Nucleotide‐Gated Cation Channels on Bladder Afferent Sensory Transmission
ABSTRACT ObjectiveThis study aimed to investigate the potential role of cesium chloride (CsCl), ivabradine (IVA), and isoproterenol (ISO) on the sensory transmission of bladder afferents to graded urinary bladder distension (UBD). We specifically selected these drugs to target the hyperpolarization‐activated cyclic nucleotide‐gated (HCN) cation channels to determine their role in afferent encoding. MethodsThe bladders of C57BL/6 female mice were harvested with attached pelvic nerves in continuity, and the stimulus–response function (SRF) of bladder afferents to stepped bladder distension (20, 40, 60, 80 cmH2O) was recorded by single‐fiber recordings. Their changes in SRF to bath application of CsCl, IVA, and ISO were then evaluated. The presence of HCN on bladder afferent endings was assessed through immunohistological staining on bladder sections from mice with genetically labeled bladder afferents. ResultsIVA and ISO did not significantly reduce afferent responses to UBD, whereas CsCl increased afferent responses. Bladder afferents in the pelvic nerve pathway were categorized into low‐firing (LF, < 10 Hz) and high‐firing (HF, > 10 Hz) groups. SRF in both the LF and HF groups showed similar trends with no significant changes in response to IVA and ISO. CsCl increased SRF only in the HF group but not in the LF group. Immunohistological staining revealed that HCN1 does not extensively co‐localize with afferent endings, showing only sporadic presence. ConclusionOur targeted pharmacological studies with single‐fiber recordings and immunohistological staining collectively suggest that HCN channels do not play a significant role in bladder afferent sensory transmission.
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- Award ID(s):
- 1844762
- PAR ID:
- 10628339
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- LUTS: Lower Urinary Tract Symptoms
- Volume:
- 17
- Issue:
- 5
- ISSN:
- 1757-5664
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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