Biology subjects

Heppner, T. J.

Publications and source records attributed to Heppner, T. J..

3 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

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↗

bioRxiv2021

Electro-Metabolic Sensing Through Capillary ATP-Sensitive K+ Channels and Adenosine to Control Cerebral Blood Flow

The dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuro/glial-derived compounds that regulate regional and global cerebral perfusion. The membrane potential (VM) of vascular cells serves as the essential output in this scenario, linking brain activity to vascular function. The ATP-sensitive K+ channel (KATP) is a key regulator of vascular VM in other beds, but whether brain capillaries possess functional KATP channels remains unknown. Here, we demonstrate that brain capillary ECs and pericytes express KATP channels that robustly control VM. We further show that the endogenous mediator adenosine acts through A2A receptors and the Gs/cAMP/PKA pathway to activate capillary KATP channels. Moreover, KATP channel stimulation in vivo causes vasodilation and increases cerebral blood flow (CBF). These findings establish the presence of KATP channels in cECs and pericytes and suggest their significant influence on CBF. HIGHLIGHTSO_LICapillary network cellular components--endothelial cells and pericytes--possess functional KATP channels. C_LIO_LIActivation of KATP channels causes profound hyperpolarization of capillary cell membranes. C_LIO_LICapillary KATP channels are activated by exogenous adenosine via A2A receptors and cAMP-dependent protein kinase. C_LIO_LIKATP channel activation by adenosine or synthetic openers increases cerebral blood flow. C_LI

neuroscience↗