Role of bicarbonate in the regulation of intracellular pH in the mammalian ventricular myocyte

2002 ◽  
Vol 80 (5) ◽  
pp. 579-596 ◽  
Author(s):  
Richard D Vaughan-Jones ◽  
Kenneth W Spitzer
Keyword(s):  
Intracellular Ph ◽  
Cardiac Contractility ◽  
Physiological Role ◽  
Cardiac Cells ◽  
Whole Body ◽  
Bicarbonate Transport ◽  
Acid Base ◽  
Bicarbonate Transporter ◽  
Coupling Protein

Bicarbonate is important for pHi control in cardiac cells. It is a major part of the intracellular buffer apparatus, it is a substrate for sarcolemmal acid-equivalent transporters that regulate intracellular pH, and it contributes to the pHo sensitivity of steady-state pHi, a phenomenon that may form part of a whole-body response to acid/base disturbances. Both bicarbonate and H+/OH– transporters participate in the sarcolemmal regulation of pHi, namely Na+–HCO3– cotransport (NBC), Cl––HCO3– exchange (i.e., anion exchange, AE), Na+–H+ exchange (NHE), and Cl––OH– exchange (CHE). These transporters are coupled functionally through changes of pHi, while pHi is linked to [Ca2+]i through secondary changes in [Na+]i mediated by NBC and NHE. Via such coupling, decreases of pHo and pHi can ultimately lead to an elevation of [Ca2+]i, thereby influencing cardiac contractility and electrical rhythm. Bicarbonate is also an essential component of an intracellular carbonic buffer shuttle that diffusively couples cytoplasmic pH to the sarcolemma and minimises the formation of intracellular pH microdomains. The importance of bicarbonate is closely linked to the activity of the enzyme carbonic anhydrase (CA). Without CA activity, intracellular bicarbonate-dependent buffering, membrane bicarbonate transport, and the carbonic shuttle are severely compromised. There is a functional partnership between CA and HCO3– transport. Based on our observations on intracellular acid mobility, we propose that one physiological role for CA is to act as a pH-coupling protein, linking bulk pH to the allosteric H+ control sites on sarcolemmal acid/base transporters.Key words: bicarbonate transporter, pHi, heart, ventricular.

scholarly journals The Role of Adenine Nucleotide Translocase in the Assembly of Respiratory Supercomplexes in Cardiac Cells

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1247 ◽  
Author(s):  
Rebecca M. Parodi-Rullán ◽  
Xavier Chapa-Dubocq ◽  
Roberto Guzmán-Hernández ◽  
Sehwan Jang ◽  
Carlos A. Torres-Ramos ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Adenine Nucleotide ◽  
Physiological Role ◽  
Cardiac Cells ◽  
Adenine Nucleotide Translocase ◽  
Inner Mitochondrial Membrane ◽  
Chain Complexes ◽  
Transport Chain ◽  
H9c2 Cardiomyoblasts

Individual electron transport chain complexes have been shown to assemble into the supramolecular structures known as the respiratory chain supercomplexes (RCS). Several studies reported an associative link between RCS disintegration and human diseases, although the physiological role, structural integrity, and mechanisms of RCS formation remain unknown. Our previous studies suggested that the adenine nucleotide translocase (ANT), the most abundant protein of the inner mitochondrial membrane, can be involved in RCS assembly. In this study, we sought to elucidate whether ANT knockdown (KD) affects RCS formation in H9c2 cardiomyoblasts. Results showed that genetic silencing of ANT1, the main ANT isoform in cardiac cells, stimulated proliferation of H9c2 cardiomyoblasts with no effect on cell viability. ANT1 KD reduced the ΔΨm but increased total cellular ATP levels and stimulated the production of total, but not mitochondrial, reactive oxygen species. Importantly, downregulation of ANT1 had no significant effects on the enzymatic activity of individual ETC complexes I–IV; however, RCS disintegration was stimulated in ANT1 KD cells as evidenced by reduced levels of respirasome, the main RCS. The effects of ANT1 KD to induce RCS disassembly was not associated with acetylation of the exchanger. In conclusion, our study demonstrates that ANT is involved in RCS assembly.

Vascular development in chick embryos: a possible role for adenosine

1989 ◽  
Vol 256 (1) ◽  
pp. H240-H246 ◽  
Author(s):  
T. H. Adair ◽  
J. P. Montani ◽  
D. M. Strick ◽  
A. C. Guyton
Keyword(s):  
Growth Regulation ◽  
Vascular System ◽  
Biological Effects ◽  
Physiological Role ◽  
Ringer Solution ◽  
Whole Body ◽  
Chick Embryos ◽  
Endogenous Adenosine ◽  
Maximum Decrease

We studied the possible role of adenosine in the development of the vasculature using 217 chick embryos. Adenosine (2-32 mumol/day), inosine (16 mumol/day), dipyridamole (0.04-0.4 mumol/day), or aminophylline (400 and 800 micrograms/day) were administered twice each day into the air space on days 11-14. Control embryos received Ringer solution. Whole body vascularity was estimated on day 15 as the whole body structural vascular resistance (SVR), i.e., the hydraulic resistance of the maximally dilated vasculature. Adenosine decreased the SVR in a dose-related manner at the lower dosage amounts but caused a maximum decrease in SVR at the higher dosage amounts averaging 30% below the Ringer control values. Equimolar amounts of adenosine and inosine decreased the SVR by the same extent. Dipyridamole, which potentiates the biological effects of endogenous adenosine, also decreased the SVR in a dose-related manner to values averaging approximately 30% below control. When the effects of endogenous adenosine were blocked by aminophylline, the SVR increased in a dose-related manner to approximately 100% above control at the highest dosage amount. These results suggest that adenosine could have a physiological role in growth regulation of the vascular system in the chick embryo.

scholarly journals Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Audrey Sambeat ◽  
Joanna Ratajczak ◽  
Magali Joffraud ◽  
José L. Sanchez-Garcia ◽  
Maria P. Giner ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Physiological Role ◽  
Whole Body ◽  
Nicotinamide Riboside ◽  
Hepatic Cells ◽  
Broad Array ◽  
Rate Limiting ◽  
Fat Feeding ◽  
Deficient Mice

Abstract Supplementation with the NAD+ precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD+ synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD+ levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders.

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoKATP in response to inotropic stress

2006 ◽  
Vol 291 (1) ◽  
pp. H152-H160 ◽  
Author(s):  
Keith D. Garlid ◽  
Paolo E. Puddu ◽  
Philippe Pasdois ◽  
Alexandre D. T. Costa ◽  
Bertrand Beauvoit ◽  
...  
Keyword(s):  
Adenine Nucleotide ◽  
Cardiac Contractility ◽  
Physiological Role ◽  
Rate Pressure Product ◽  
Half Saturation Constant ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Permeabilized Fibers ◽  
High Work

This study investigates the role of the mitochondrial ATP-sensitive K+ channel (mitoKATP) in response to positive inotropic stress. In Langendorff-perfused rat hearts, inotropy was induced by increasing perfusate calcium to 4 mM, by adding 80 μM ouabain or 0.25 μM dobutamine. Each of these treatments resulted in a sustained increase in rate-pressure product (RPP) of ∼60%. Inhibition of mitoKATP by perfusion of 5-hydroxydecanoate (5-HD) or tetraphenylphosphonium before induction of inotropic stress resulted in a marked attenuation of RPP. Inhibition of mitoKATP after induction of stress caused the inability of the heart to maintain a high-work state. In human atrial fibers, the increase in contractility induced by dobutamine was inhibited 60% by 5-HD. In permeabilized fibers from the Langendorff-perfused rat hearts, inhibition of mitoKATP resulted, in all cases, in an alteration of adenine nucleotide compartmentation, as reflected by a 60% decrease in the half-saturation constant for ADP [ K1/2 (ADP)]. We conclude that opening of cardiac mitoKATP is essential for an appropriate response to positive inotropic stress and propose that its involvement proceeds through the prevention of stress-induced decrease in mitochondrial matrix volume. These results indicate a physiological role for mitoKATP in inotropy and, by extension, in heart failure.

The role of the amphibian kidney and bladder in the regulation of acid–base relevant ions

1989 ◽  
Vol 67 (12) ◽  
pp. 3064-3069 ◽  
Author(s):  
Daniel P. Toews ◽  
Daniel F. Stiffler
Keyword(s):  
Animal Studies ◽  
Intact Animal ◽  
Bladder Function ◽  
Whole Body ◽  
Transport Mechanisms ◽  
Acid Base ◽  
Cellular Mechanisms ◽  
Physiological Conditions

The amphibian bladder and kidneys have proven to be excellent structures for in vitro investigations of ion-transport mechanisms and cellular mechanisms of hormone action. Very often, however, the normal physiological conditions that exist in the intact animal have not been duplicated in the particular experimental setup. On the other hand, whole-animal studies relating to kidney and bladder function are somewhat rare because it is technically very difficult to separate the relative contributions of the kidney, bladder, and skin to processes such as whole-body acid–base regulation. In this review we attempt to describe the most significant advances of in vitro studies as they relate to acid–base regulation and to integrate these experiments with the limited number of investigations performed on whole-animal preparations.

scholarly journals Role of Na-H exchangers and vacuolar H+ pumps in intracellular pH regulation in neonatal rat osteoclasts.

1995 ◽  
Vol 105 (2) ◽  
pp. 177-208 ◽  
Author(s):  
J H Ravesloot ◽  
T Eisen ◽  
R Baron ◽  
W F Boron
Keyword(s):  
Intracellular Ph ◽  
Imaging System ◽  
Ph Regulation ◽  
Neonatal Rat ◽  
Hill Coefficient ◽  
Acid Base ◽  
Buffering Power ◽  
Acid Extrusion

Osteoclasts resorb bone by pumping of H+ into a compartment between the cell and the bone surface. Intracellular pH (pHi) homeostasis requires that this acid extrusion, mediated by a vacuolar-type H+ ATPase, be complemented by other acid-base transporters. We investigated acid-extrusion mechanisms of single, freshly isolated, neonatal rat osteoclasts. Cells adherent to glass coverslips were studied in the nominal absence of CO2/HCO3-, using the pH-sensitive dye BCECF and a digital imaging system. Initial pHi averaged 7.31 and was uniform throughout individual cells. Intrinsic buffering power (beta 1) decreased curvilinearly from approximately 25 mM at pHi = 6.4 to approximately 6.0 mM at pHi = 7.4. In all polygonally shaped osteoclasts, and approximately 60% of round osteoclasts (approximately 20% of total), pHi recovery from acid loads was mediated exclusively by Na-H exchange. In these pattern-1 cells, pHi recovery was 95% complete within 200 s, and was blocked by removing Na+, or by applying 1 mM amiloride, 50 microM ethylisopropylamiloride (EIPA), or 50 microM hexamethyleneamiloride (HMA). The apparent K1/2 for HMA ([Na+]o = 150 mM) was 49 nM, and the apparent K1/2 for Na+ was 45 mM. Na-H exchange, corrected for amiloride-insensitive fluxes, was half maximal at pHi 6.73, with an apparent Hill coefficient for intracellular H+ of 2.9. Maximal Na-H exchange averaged 741 microM/s. In the remaining approximately 40% of round osteoclasts (pattern-2 cells), pHi recovery from acid loads was brisk even in the absence of Na+ or presence of amiloride. This Na(+)-independent pHi recovery was blocked by 7-chloro-4-nitrobenz-2-oxa-1,3-diazol (NBD-Cl), a vacuolar-type H+ pump inhibitor. Corrected for NBD-Cl insensitive fluxes, H+ pump fluxes decreased approximately linearly from 96 at pHi 6.8 to 11 microM/s at pHi 7.45. In approximately 45% of pattern-2 cells, Na+ readdition elicited a further pHi recovery, suggesting that H+ pumps and Na-H exchangers can exist simultaneously. We conclude that, under the conditions of our study, most neonatal rat osteoclasts express Na-H exchangers that are probably of the ubiquitous basolateral subtype. Some cells express vacuolar-type H+ pumps in their plasma membrane, as do active osteoclasts in situ.

scholarly journals Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

2020 ◽  
Vol 10 (9) ◽  
pp. 583
Author(s):  
Patrick S. Hosford ◽  
Natalia Ninkina ◽  
Vladimir L. Buchman ◽  
Jeffrey C. Smith ◽  
Nephtali Marina ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Physiological Role ◽  
Normal Function ◽  
Whole Body ◽  
Cardiovascular Reflexes ◽  
Long Term Effects ◽  
Gene Encoding ◽  
Age Related

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.

scholarly journals Physiological role of NBCe2 in the regulation of electrolyte transport in the distal nephron

2015 ◽  
Vol 309 (6) ◽  
pp. F489-F491 ◽  
Author(s):  
Donghai Wen ◽  
Steven C. Sansom
Keyword(s):  
Blood Pressure ◽  
Potential Function ◽  
Physiological Role ◽  
Electrolyte Transport ◽  
Distal Nephron ◽  
Acid Base ◽  
Renal Electrolyte Transport ◽  
Regulation Of Blood Pressure

The electrogenic Na+-HCO3− cotransporter 2 (NBCe2) is a newly discovered protein in the distal nephron. Our understanding is minimal regarding its physiological role in renal electrolyte transport. In this mini-review, we summarize the potential function of NBCe2 in the regulation of blood pressure, acid-base, and K+ and Ca2+ transport in the distal nephron.

scholarly journals The Bicarbonate Transporter (MoAE4) Localized on Both Cytomembrane and Tonoplast Promotes Pathogenesis in Magnaporthe oryzae

2021 ◽  
Vol 7 (11) ◽  
pp. 955
Author(s):  
Yuejia Dang ◽  
Yi Wei ◽  
Penghui Zhang ◽  
Xinchun Liu ◽  
Xinrui Li ◽  
...  
Keyword(s):  
Magnaporthe Oryzae ◽  
Drug Target ◽  
Blast Disease ◽  
Bicarbonate Transport ◽  
Bicarbonate Transporter ◽  
Physiological Processes ◽  
Transporter Family ◽  
The Common ◽  
Group Member

Bicarbonate (HCO3−) transporter family including the anion exchanger (AE) group is involved in multiple physiological processes through regulating acid-base homeostasis. HCO3− transporters have been extensively studied in mammals, but fungal homologues of AE are poorly understood. Here, we characterized the AE group member (MoAE4) in Magnaporthe oryzae. MoAE4 exhibits more sequence and structure homologies with the reported AE4 and BOR1 proteins. In addition to the common sublocalization on cytomembrane, MoAE4 also localizes on tonoplast. Yeast complementation verified that MoAE4 rescues boron sensitivity and endows NaHCO3 tolerance in the BOR1 deleted yeast. MoAE4 gene is bicarbonate induced in M. oryzae; and loss of MoAE4 (ΔMoAE4) resulted in mycelial growth inhibited by NaHCO3. Lucigenin fluorescence quenching assay confirmed that ΔMoAE4 accumulated less HCO3− in vacuole and more HCO3− in cytosol, revealing a real role of MoAE4 in bicarbonate transport. ΔMoAE4 was defective in conidiation, appressorium formation, and pathogenicity. More H2O2 was detected to be accumulated in ΔMoAE4 mycelia and infected rice cells. Summarily, our data delineate a cytomembrane and tonoplast located HCO3− transporter, which is required for development and pathogenicity in M. oryzae, and revealing a potential drug target for blast disease control.

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