tissue acidosis
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Author(s):  
Daniel W. Montgomery ◽  
Garfield T. Kwan ◽  
William G. Davison ◽  
Jennifer Finlay ◽  
Alex Berry ◽  
...  

Fish in coastal ecosystems can be exposed to acute variations in CO2 of between 0.2-1 kPa CO2 (2,000 - 10,000 µatm). Coping with this environmental challenge will depend on the ability to rapidly compensate the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon sudden exposure to ∼1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ∼40 minutes, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ∼2 hours, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3− in blood, which increased from ∼4 to ∼22 mM. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3− and pH, likely because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments.


2021 ◽  
Vol 15 ◽  
Author(s):  
Victoria S. Foster ◽  
Lachlan D. Rash ◽  
Glenn F. King ◽  
Michelle M. Rank

Peripheral and central immune cells are critical for fighting disease, but they can also play a pivotal role in the onset and/or progression of a variety of neurological conditions that affect the central nervous system (CNS). Tissue acidosis is often present in CNS pathologies such as multiple sclerosis, epileptic seizures, and depression, and local pH is also reduced during periods of ischemia following stroke, traumatic brain injury, and spinal cord injury. These pathological increases in extracellular acidity can activate a class of proton-gated channels known as acid-sensing ion channels (ASICs). ASICs have been primarily studied due to their ubiquitous expression throughout the nervous system, but it is less well recognized that they are also found in various types of immune cells. In this review, we explore what is currently known about the expression of ASICs in both peripheral and CNS-resident immune cells, and how channel activation during pathological tissue acidosis may lead to altered immune cell function that in turn modulates inflammatory pathology in the CNS. We identify gaps in the literature where ASICs and immune cell function has not been characterized, such as neurotrauma. Knowledge of the contribution of ASICs to immune cell function in neuropathology will be critical for determining whether the therapeutic benefits of ASIC inhibition might be due in part to an effect on immune cells.


2021 ◽  
Author(s):  
Daniel W. Montgomery ◽  
Garfield T. Kwan ◽  
William G. Davison ◽  
Jennifer Finlay ◽  
Alex Berry ◽  
...  

AbstractFish in coastal ecosystems can be exposed to acute variations in CO2that can approach 1 kPa CO2(10,000 μatm). Coping with this environmental challenge will depend on the ability to rapidly compensate the internal acid-base disturbance caused by sudden exposure to high environmental CO2(blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon exposure to ~1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ~40 minutes, thus restoring haemoglobin-O2affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ~2 hours, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3− in blood, which increased from ~4 to ~22 mM. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2exposure occurred in seawater with experimentally reduced HCO3− and pH, likely because reduced environmental pH inhibited gill H+excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2fluctuations that naturally occur in coastal environments.Summary statementEuropean sea bass exposed to 1 kPa (10,000 μatm) CO2regulate blood and red cell pH within 2 hours and 40 minutes, respectively, protecting O2transport capacity, via enhanced gill acid excretion.


2021 ◽  
Vol 19 ◽  
Author(s):  
Yu Cheng ◽  
Wuqiong Zhang ◽  
Yue Li ◽  
Ting Jiang ◽  
Buhajar Mamat ◽  
...  

Background: Epilepsy represents one of the most common brain diseases among humans. Tissue acidosis is a common phenomenon in epileptogenic foci. This said, its roles in epileptogenesis remain unclear. Acid-sensing ion channel-1a (ASIC1a) represents a potential way to assess new therapies. ASIC1a, mainly expressed in the mammalian brain, is a type of protein-gated cation channel. It has been shown to play an important role in the pathological mechanism of various diseases, including stroke, epilepsy, and multiple sclerosis. Methods: Data were collected from Web of Science, Medline, PubMed, through searching for these keywords: "Acid-sensing ion channels 1a" or "ASIC1a" and "epilepsy" or "seizure". Results: The role of ASIC1a in epilepsy remains controversial; it may represent a promising therapeutic target of epilepsy. Conclusion:This review is intended to provide an overview of the structure, trafficking, and molecular mechanisms of ASIC1a in order to further elucidate the role of ASIC1a in epilepsy.


Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 460
Author(s):  
Orsolya M. Tóth ◽  
Ákos Menyhárt ◽  
Rita Frank ◽  
Dóra Hantosi ◽  
Eszter Farkas ◽  
...  

Ischemic stroke is a leading cause of death and disability worldwide. Yet, the effective therapy of focal cerebral ischemia has been an unresolved challenge. We propose here that ischemic tissue acidosis, a sensitive metabolic indicator of injury progression in cerebral ischemia, can be harnessed for the targeted delivery of neuroprotective agents. Ischemic tissue acidosis, which represents the accumulation of lactic acid in malperfused brain tissue is significantly exacerbated by the recurrence of spreading depolarizations. Deepening acidosis itself activates specific ion channels to cause neurotoxic cellular Ca2+ accumulation and cytotoxic edema. These processes are thought to contribute to the loss of the ischemic penumbra. The unique metabolic status of the ischemic penumbra has been exploited to identify the penumbra zone with imaging tools. Importantly, acidosis in the ischemic penumbra may also be used to guide therapeutic intervention. Agents with neuroprotective promise are suggested here to be delivered selectively to the ischemic penumbra with pH-responsive smart nanosystems. The administered nanoparticels release their cargo in acidic tissue environment, which reliably delineates sites at risk of injury. Therefore, tissue pH-targeted drug delivery is expected to enrich sites of ongoing injury with the therapeutical agent, without the risk of unfavorable off-target effects.


Talanta ◽  
2020 ◽  
pp. 122045
Author(s):  
Samuel Dulay ◽  
Lourdes Rivas ◽  
Sandrine Miserere ◽  
Laura Pla ◽  
Sergio Berdún ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2484 ◽  
Author(s):  
Zoltán Pethő ◽  
Karolina Najder ◽  
Tiago Carvalho ◽  
Roisin McMorrow ◽  
Luca Matteo Todesca ◽  
...  

Tissue acidosis plays a pivotal role in tumor progression: in particular, interstitial acidosis promotes tumor cell invasion, and is a major contributor to the dysregulation of tumor immunity and tumor stromal cells. The cell membrane and integral membrane proteins commonly act as important sensors and transducers of altered pH. Cell adhesion molecules and cation channels are prominent membrane proteins, the majority of which is regulated by protons. The pathophysiological consequences of proton-sensitive ion channel function in cancer, however, are scarcely considered in the literature. Thus, the main focus of this review is to highlight possible events in tumor progression and tumor immunity where the pH sensitivity of cation channels could be of great importance.


2020 ◽  
Vol 162 ◽  
pp. 107850 ◽  
Author(s):  
Orsolya M. Tóth ◽  
Ákos Menyhárt ◽  
Viktória Éva Varga ◽  
Dóra Hantosi ◽  
Orsolya Ivánkovits-Kiss ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Friedrich Baark ◽  
Fiona Shaughnessy ◽  
Victoria R. Pell ◽  
James E. Clark ◽  
Thomas R. Eykyn ◽  
...  

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