scholarly journals Blockade of Acid-Sensing Ion Channels Increases Urinary Bladder Capacity With or Without Intravesical Irritation in Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Mitsuharu Yoshiyama ◽  
Hideki Kobayashi ◽  
Masayuki Takeda ◽  
Isao Araki
Keyword(s):  
Acetic Acid ◽  
Ion Channels ◽  
Urinary Bladder ◽  
Bladder Capacity ◽  
Saline Infusion ◽  
Acid Sensing Ion Channels ◽  
Vehicle Injection ◽  
The Central Nervous System ◽  
Bladder Activity

We conducted this study to examine whether acid-sensing ion channels (ASICs) are involved in the modulation of urinary bladder activity with or without intravesical irritation induced by acetic acid. All in vivo evaluations were conducted during continuous infusion cystometry in decerebrated unanesthetized female mice. During cystometry with a pH 6.3 saline infusion, an i.p. injection of 30 μmol/kg A-317567 (a potent, non-amiloride ASIC blocker) increased the intercontraction interval (ICI) by 30% (P < 0.001), whereas vehicle injection had no effect. An intravesical acetic acid (pH 3.0) infusion induced bladder hyperactivity, with reductions in ICI and maximal voiding pressure (MVP) by 79% (P < 0.0001) and 29% (P < 0.001), respectively. A-317567 (30 μmol/kg i.p.) alleviated hyperreflexia by increasing the acid-shortened ICI by 76% (P < 0.001). This dose produced no effect on MVP under either intravesical pH condition. Further analysis in comparison with vehicle showed that the increase in ICI (or bladder capacity) by the drug was not dependent on bladder compliance. Meanwhile, intravesical perfusion of A-317567 (100 μM) had no effect on bladder activity during pH 6.0 saline infusion cystometry, and drug perfusion at neither 100 μM nor 1 mM produced any effects on bladder hyperreflexia during pH 3.0 acetic acid infusion cystometry. A-317567 has been suggested to display extremely poor penetrability into the central nervous system and thus to be a peripherally active blocker. Taken together, our results suggest that blockade of ASIC signal transduction increases bladder capacity under normal intravesical pH conditions and alleviates bladder hyperreflexia induced by intravesical acidification and that the site responsible for this action is likely to be the dorsal root ganglia.

scholarly journals Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy

2016 ◽  
Vol 371 (1700) ◽  
pp. 20150431 ◽  
Author(s):  
O. Ievglevskyi ◽  
D. Isaev ◽  
O. Netsyk ◽  
A. Romanov ◽  
M. Fedoriuk ◽  
...  
Keyword(s):  
Ion Channels ◽  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Synaptic Activity ◽  
Mammalian Brain ◽  
Strong Increase ◽  
Life And Death ◽  
Acid Sensing Ion Channels

Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca 2+ -permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg 2+ model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus in vivo . Our results reveal a significant novel role for ASICs. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.

CONTRIBUTION OF ACID-SENSING ION CHANNELS TO GENDER DIFFERENCE IN MOUSE BLADDER RESPONSE TO ACETIC ACID: A NOVEL CANDIDATE FOR INTERSTITIAL CYSTITIS PATHOGENESIS

2008 ◽  
Vol 179 (4S) ◽  
pp. 129-130 ◽  
Author(s):  
Hideki Kobayashi ◽  
Mitsuharu Yoshiyama ◽  
Isao Araki ◽  
Hidenori Zakoji ◽  
Norifumi Sawada ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Ion Channels ◽  
Gender Difference ◽  
Interstitial Cystitis ◽  
Acid Sensing Ion Channels

scholarly journals Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes

2018 ◽  
Vol 115 (33) ◽  
pp. 8430-8435 ◽  
Author(s):  
Timothy Lynagh ◽  
Yana Mikhaleva ◽  
Janne M. Colding ◽  
Joel C. Glover ◽  
Stephan A. Pless
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Sodium Current ◽  
Oikopleura Dioica ◽  
Acid Sensing Ion Channels ◽  
Mammalian Lineage ◽  
Molecular Determinants ◽  
Animal Phyla ◽  
The Central Nervous System ◽  
Functionally Diverse

Acid-sensing ion channels (ASICs) are proton-gated ion channels broadly expressed in the vertebrate nervous system, converting decreased extracellular pH into excitatory sodium current. ASICs were previously thought to be a vertebrate-specific branch of the DEG/ENaC family, a broadly conserved but functionally diverse family of channels. Here, we provide phylogenetic and experimental evidence that ASICs are conserved throughout deuterostome animals, showing that ASICs evolved over 600 million years ago. We also provide evidence of ASIC expression in the central nervous system of the tunicate, Oikopleura dioica. Furthermore, by comparing broadly related ASICs, we identify key molecular determinants of proton sensitivity and establish that proton sensitivity of the ASIC4 isoform was lost in the mammalian lineage. Taken together, these results suggest that contributions of ASICs to neuronal function may also be conserved broadly in numerous animal phyla.

Neural pathways involved in sacral neuromodulation of reflex bladder activity in cats

2013 ◽  
Vol 304 (6) ◽  
pp. F710-F717 ◽  
Author(s):  
Fan Zhang ◽  
Shouguo Zhao ◽  
Bing Shen ◽  
Jicheng Wang ◽  
Dwight E. Nelson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Sacral Neuromodulation ◽  
Bladder Capacity ◽  
Inhibitory Effect ◽  
Ventral Root ◽  
Neural Pathways ◽  
Descending Pathways ◽  
The Central Nervous System ◽  
Bladder Activity ◽  
Stimulation Of

This study examined the mechanisms underlying the effects of sacral neuromodulation on reflex bladder activity in chloralose-anesthetized cats. Bladder activity was recorded during cystometrograms (CMGs) or under isovolumetric conditions. An S1–S3 dorsal (DRT) or ventral root (VRT) was electrically stimulated at a range of frequencies (1–30 Hz) and at intensities relative to threshold (0.25–2T) for evoking anal/toe twitches. Stimulation of DRTs but not VRTs at 1T intensity and frequencies of 1–30 Hz inhibited isovolumetric rhythmic bladder contractions. A 5-Hz DRT stimulation during CMGs was optimal for increasing ( P < 0.05) bladder capacity (BC), but stimulation at 15 and 30 Hz was ineffective. Stimulation of the S1 DRT was more effective (increases BC to 144% and 164% of control at 1T and 2T, respectively) than S2 DRT stimulation (increases BC to 132% and 150% of control). Bilateral transection of the hypogastric or pudendal nerves did not change the inhibitory effect induced by S1 DRT stimulation. Repeated stimulation of S1 and S2 DRTs during multiple CMGs elicited a significant ( P < 0.05) increase in BC (to 155 ± 11% of control) that persisted after termination of the stimulation. These results in cats suggest that the inhibition of reflex bladder activity by sacral neuromodulation occurs primarily in the central nervous system by inhibiting the ascending or descending pathways of the spinobulbospinal micturition reflex.

scholarly journals Acid-Sensing Ion Channels and Mechanosensation

2021 ◽  
Vol 22 (9) ◽  
pp. 4810
Author(s):  
Nina Ruan ◽  
Jacob Tribble ◽  
Andrew M. Peterson ◽  
Qian Jiang ◽  
John Q. Wang ◽  
...  
Keyword(s):  
Ion Channels ◽  
Underlying Mechanism ◽  
Cation Channels ◽  
Ischemic Brain Injury ◽  
Mechanical Forces ◽  
Sodium Permeability ◽  
Ischemic Brain ◽  
Acid Sensing Ion Channels ◽  
The Central Nervous System ◽  
Spring Mechanism

Acid-sensing ion channels (ASICs) are mainly proton-gated cation channels that are activated by pH drops and nonproton ligands. They are part of the degenerin/epithelial sodium channel superfamily due to their sodium permeability. Predominantly expressed in the central nervous system, ASICs are involved in synaptic plasticity, learning/memory, and fear conditioning. These channels have also been implicated in multiple disease conditions, including ischemic brain injury, multiple sclerosis, Alzheimer’s disease, and drug addiction. Recent research has illustrated the involvement of ASICs in mechanosensation. Mechanosensation is a form of signal transduction in which mechanical forces are converted into neuronal signals. Specific mechanosensitive functions have been elucidated in functional ASIC1a, ASIC1b, ASIC2a, and ASIC3. The implications of mechanosensation in ASICs indicate their subsequent involvement in functions such as maintaining blood pressure, modulating the gastrointestinal function, and bladder micturition, and contributing to nociception. The underlying mechanism of ASIC mechanosensation is the tether-gate model, which uses a gating-spring mechanism to activate ASIC responses. Further understanding of the mechanism of ASICs will help in treatments for ASIC-related pathologies. Along with the well-known chemosensitive functions of ASICs, emerging evidence has revealed that mechanosensitive functions of ASICs are important for maintaining homeostasis and contribute to various disease conditions.

scholarly journals Effects of Goshajinkigan (Niu-Che-Sen-Qi-Wan) for Resiniferatoxin-Sensitive Afferents on Detrusor Overactivity Induced by Acetic Acid in Conscious Rats

2006 ◽  
Vol 34 (02) ◽  
pp. 285-293 ◽  
Author(s):  
Xiaoyang Zhang ◽  
Osamu Ishizuka ◽  
Tomoaki Tanabe ◽  
Tomoya Satoh ◽  
Tsuyoshi Nakayama ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Bladder Capacity ◽  
Intravesical Instillation ◽  
Normal Diet ◽  
Intravesical Administration ◽  
Conscious Rats ◽  
C Fiber ◽  
Vehicle Injection ◽  
Micturition Volume ◽  
Normal Food

This study was performed to investigate the effects of goshajinkigan, a traditional Chinese herbal mixture, in conscious rats undergoing continuous cystometry. Systemic resiniferatoxin (RTX) pretreatment can block resiniferatoxin-sensitive (C-fiber) nerve-mediated bladder overactivity, such as that induced by intravesical administration of acetic acid. The effects of pretreatment with goshajinkigan and RTX alone or in combination on acetic acid-induced bladder overactivity in conscious rats were also compared. Female SD rats were divided into four groups. Groups 1 and 3 received normal food for 4 weeks, while groups 2 and 4 received goshajinkigan (0.09 g/kg/day) during the same period. Two days after bladder catheterization, groups 3 and 4 received RTX (0.3 mg/kg) injection, while groups 1 and 2 received vehicle alone. Cystometric investigations were performed on all animals 24 hours after RTX or vehicle injection. The effects of intravesical instillation of acetic acid ( pH = 4.0) were compared with those of intravesical saline. Goshajinkigan significantly increased threshold pressure, voiding interval, micturition volume, and bladder capacity. Intravesical instillation of acetic acid induced bladder overactivity in both normal rats and in those pretreated with goshajinkigan. However, the effects of acetic acid on voiding interval and micturition volume were significantly different between rats given normal diet and those pretreated with goshajinkigan. The effect of acetic acid was not different between goshajinkigan- and RTX-pretreated rats. The results of the present study indicated that goshajinkigan increases voiding interval, micturition volume, and bladder capacity, and pretreatment with goshajinkigan partially blocks the bladder overactivity induced by intravesical administration of acetic acid in rats.

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