Biology subjects

Hennig, G. W.

Publications and source records attributed to Hennig, G. W..

4 recordsLinked to original sources

bioRxiv2026

G-protein coupled receptor activity mediates detrusor smooth muscle phasic contractility through regulation of membrane potential

The urinary bladder functions to store and release urine, yet how the sensation of bladder fullness is conveyed and perceived to the central nervous system is not understood. During bladder filling, the detrusor smooth muscle (DSM) generates phasic contractions, resulting in pressure fluctuations within the bladder. These transient pressure events drive bursts of afferent nerve activity, yet the underlying mechanism leading to rhythmic contractions remains unclear. Here, we examined the role of Gq protein-coupled receptor (GqPCR) activity on DSM excitability and contractility. Using ex vivo pressurized urinary bladder preparations and sharp microelectrode experiments on bladder strips from mice, we evaluated whole bladder transient pressure events, whole bladder DSM Ca2+ activity, and membrane potential in bladder strips. We found that global inhibition of urinary bladder GqPCR activity with YM-254890 abates phasic contractility and transient pressure events through a reduction in DSM Ca2+ activity and propagation of Ca2+ waves. Further, we found inhibition of GqPCR significantly hyperpolarizes DSM, reducing action potentials and decreasing excitability, and activation of protein kinase C restores membrane potential to baseline levels. These findings highlight that GqPCR activity mediates DSM excitability and contractility in such a way as to result in phasic detrusor contractions and transient pressure events.

physiology↗

bioRxiv2025

Purinergic signalling and calcium dynamics: potential drivers in the onset of coordinated intestinal motility in human fetal development

Background and aimsIntestinal motility relies on inputs from multiple cells within a complex neuromuscular syncytium located in the gut wall. While it is known that motility is dependent on the development of motor patterns which govern coordinated contractile activity within the gut wall, knowledge regarding the onset of coordinated motor activity in humans is still lacking. This study assessed the emergence of coordinated motor patterns, and the molecular mechanisms underpinning developing motility, in the human fetal gut. MethodsHuman fetal gut samples (obtained via the MRC-Wellcome Trust Human Developmental Biology Resource-UK) were characterised by live imaging, spatiotemporal mapping, immunohistochemistry and RNAseq. ResultsHuman small intestinal samples displayed the presence of key cell types including enteric neurons, interstitial cells of Cajal, platelet-derived growth factor receptor alpha positive (PDGFR+) cells and smooth muscle at post conception week (PCW) 12. Between PCW12 and PCW16, functional assessment revealed a marked increase in the velocity (p= 0.0341) of propagating contractions. Subsequently, between PCW16 and PCW20 the number of contraction initiation sites reduced drastically (p=0.0053), enabling the emergence of long-distance propagating contractions. Expression analyses showed the development of coordinated motor activity was coincident with increased expression of various genes involved in calcium and purinergic signalling pathways. ConclusionsThese findings provide the first direct mechanistic evidence of the temporal development of coordinated contractile activity in the human fetal intestine, highlighting the role of calcium dynamics, purinergic signalling and interstitial cells in early stages of human motility development, potentially informing an improved understanding of the pathogenesis of gut motility disorders.

developmental biology↗

bioRxiv2025

Adenosine and acute low oxygen conditions suppress urinary bladder contractility through the activation of adenosine 2B receptors and large-conductance calcium-activated potassium channels

Under healthy conditions the urinary bladder undergoes relatively long periods of filling with well-spaced voiding events to ensure proper storage and removal of urine respectively. During the filling phase, distinct contractile events in detrusor urinary smooth muscle (UBSM) elicit transient non-voiding pressure events and associated bursts in afferent nerve activity to relay the sensation of bladder fullness. The mechanisms that regulate UBSM excitability and associated non-voiding pressure events under physiological and pathological conditions are poorly understood. Here we investigated the role of adenosine signaling in regulating urinary bladder contractility. Using an ex vivo pressurized bladder preparation from mice and patch-clamp electrophysiology in isolated UBSM we evaluated whole bladder transient pressure events, whole bladder detrusor Ca2+ activity, and single UBSM ion channel activity. We found that adenosine suppresses bladder activity through activation of A2B adenosine receptors and downstream activation of large-conductance calcium-activated potassium (BKCa) channels. We further demonstrated that acute exposure to low oxygen conditions using a chemical oxygen scavenger potently suppresses bladder contractility through the A2B receptor pathway. These results highlight the prominent role adenosine receptors and downstream potassium channels play in regulating urinary bladder contractility in physiological and pathological contexts.

physiology↗

bioRxiv2017

Activity-induced Ca2+ signaling in perisynaptic Schwann cells is mediated by P2Y1 receptors and regulates muscle fatigue

Perisynaptic glial cells respond to neural activity by increasing cytosolic levels of calcium, but the functional significance of this pathway is unclear. Terminal/persiynaptic Schwann cells (TPSCs) are a perisynaptic glial cell at the neuromuscular junction. Here, we provide genetic evidence that neural activity-induced intracellular calcium accumulation in neonatal TPSCs is mediated exclusively by P2Y1 receptors. In P2ry1 mutant mice lacking these responses, postsynaptic, rather than presynaptic, function was altered in response to nerve stimulation. This impairment was correlated with a greater susceptibility to activity-induced muscle fatigue. Interestingly, fatigue in P2ry1 mutants was exacerbated by exposure to high potassium to a greater degree than in control mice. High potassium itself increased cytosolic levels of calcium in TPSCs, a response which was also reduced P2ry1 mutants. These results suggest that activity-induced calcium responses in perisynaptic glia at the NMJ regulate postsynaptic function and muscle fatigue by influencing the levels of perisynaptic potassium.

neuroscience↗