ASIC3 fine-tunes bladder sensory signaling

Area of Science:

• Neuroscience
• Physiology
• Molecular Biology

Background:

• Acid-sensing ion channels (ASICs) are proton-gated cation channels vital for neuronal signaling.
• ASIC3, predominantly found in sensory neurons, is implicated in mechanosensation and pain perception.

Purpose of the Study:

• To investigate the specific role of ASIC3 in bladder sensory signaling and overall bladder function.
• To determine how ASIC3 influences the response of bladder sensory neurons to changes in pH.

Main Methods:

• Electrophysiological recordings from bladder sensory neurons of wild-type (WT) and ASIC3 knockout (KO) mice.
• Analysis of ASIC-like currents evoked by extracellular acidification.
• Assessment of bladder function, including voiding volume and micturition reflex sensitivity, in WT and ASIC3 KO mice.

Main Results:

• Extracellular acidification evoked ASIC-like currents in a subset of bladder sensory neurons from both WT and KO mice.
• Absence of ASIC3 altered the kinetics of these currents, suggesting heteromeric channel assembly.
• ASIC3 deletion abolished action potential firing in response to acidification in bladder sensory neurons.
• ASIC3 knockout mice exhibited reduced voiding volume and lower pressure thresholds for micturition.

Conclusions:

• ASIC3 plays a significant role in sensing bladder filling and modulating bladder sensory signaling.
• ASIC3 influences the composition and function of ASICs in bladder afferents.
• ASIC3 is critical for normal bladder function, impacting voiding efficiency and sensory feedback.