Activation of gadolinium-sensitive ion channels in cardiomyocytes in early adaptive stages of volume overload-induced heart failure

McNicholas-Bevensee, Carmel M.; Deandrade, Kevin; Bradley, Wayne E.; Dell’Italia, Louis J.; Lucchesi, Pamela A.; Bevensee, Mark O.

doi:10.1016/j.cardiores.2006.08.001

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…Experiments were performed at room temperature (Ϸ22°C) in a flow-through chamber on the stage of an inverted DMIRB microscope (Leica) as previously described (8). Exchange of bath solutions was achieved using a VC-6 perfusion valve control system (Warner Instruments) converging onto either one 8-port manifold or 2 such manifolds upstream of a SF-77B perfusion fast-step with 2 adjacent delivery lines (Warner Instruments) (36). Currents were obtained with an Axon Instruments Axopatch 200B patch-clamp amplifier (Molecular Devices), and digitized with an Axon Instruments Digidata-1321A interface (Molecular Devices).…”

Section: Methodsmentioning

confidence: 99%

Phosphatidylinositol 4,5-bisphosphate (PIP ₂ ) stimulates the electrogenic Na/HCO ₃ cotransporter NBCe1-A expressed in Xenopus oocytes

Wu¹,

McNicholas²,

Bevensee

2009

Proc. Natl. Acad. Sci. U.S.A.

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Bicarbonate transporters are regulated by signaling molecules/ ions such as protein kinases, ATP, and Ca 2؉ . While phospholipids such as PIP2 can stimulate Na-H exchanger activity, little is known about phospholipid regulation of bicarbonate transporters. We used the patch-clamp technique to study the function and regulation of heterologously expressed rat NBCe1-A in excised macropatches from Xenopus laevis oocytes. Exposing the cytosolic side of inside-out macropatches to a 5% CO 2/33 mM HCO 3 ؊ solution elicited a mean inward current of 14 pA in 74% of macropatches attached to pipettes (؊Vp ‫؍‬ ؊60 mV) containing a low-Na ؉ , nominally HCO 3 ؊ -free solution. Ϫ transporters play important roles in intracellular pH (pH i ) regulation and ion transport in many tissues. Since the expression cloning of the first cDNA encoding a cationcoupled HCO 3 Ϫ transporter (NBCe1) from salamander kidney (1), investigators have cloned by homology and characterized the function of additional electrogenic and electroneutral NBCs, cationcoupled anion exchangers, and associated splice variants (2). NBCe1 has 3 variants (A, B, and C) that differ at their amino and/or carboxyl termini. Na-coupled HCO 3 Ϫ transporters in conjunction with anion exchangers (AEs) are members of a superfamily of bicarbonate transporters (BTs).The pH field is now poised to address new questions regarding the physiologic importance of numerous BTs. We hypothesize that proper pH i regulation and ion transport require multiple BTseach one playing a specific role under different physiologic conditions or regulatory stimuli. Classic signaling molecules, such as PKA/cAMP, PKC, Ca 2ϩ , and ATP, can modulate heterologously expressed NBCe1. Investigators have reported that phosphorylation by activated PKA (3, 4) or an increase in cytosolic Ca 2ϩ (5) can change the Na:HCO 3 Ϫ stoichiometry of the transporter. In addition, both cAMP (3) and ATP (6) appear to stimulate an NBC-mediated current, whereas PKC isoforms inhibit transporter activity (7).Other binding proteins or NBC domains can regulate transporter function. For NBCe1, the unique amino terminus of the A variant stimulates activity, whereas the different amino terminus of the B and C variants inhibits activity (8). Such automodulation may involve additional binding proteins and signaling molecules. Indeed, Shirakabe et al. (9) reported that the IP 3 receptor binding protein released with IP 3 (IRBIT) can stimulate NBCe1-B co-expressed in oocytes by binding to the transporter's amino terminus and masking an autoinhibitory domain.Very little is known about the influence of phospholipids on the activity of BTs. PIP 2 is noteworthy because in addition to its classic role as a precursor of the Ca 2ϩ -mobilizing inositol triphosphate (IP 3 ) and the kinase-activating diacylglycerol (DAG), the phosphoinositide is a signaling molecule that can regulate solute movement (10). In pioneering work, Hilgemann and Ball (11) found that PIP 2 directly stimulates both the cardiac Na-Ca exchanger and K ATP channel. Phosphoino...

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Section: Methodsmentioning

confidence: 99%

Phosphatidylinositol 4,5-bisphosphate (PIP ₂ ) stimulates the electrogenic Na/HCO ₃ cotransporter NBCe1-A expressed in Xenopus oocytes

Wu¹,

McNicholas²,

Bevensee

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Isolated heart preparation: Isolated hearts were retrogradely perfused using modified Langendorff technique as described before (McNicholas-Bevensee et al 2006;Bell et al 2011). Briefly, rats were anesthetized using 40 mg/ kg pentobarbital (i.p).…”

Section: Echocardiographymentioning

confidence: 99%

Chlorine inhalation-induced myocardial depression and failure

et al. 2015

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Victims of chlorine (Cl2) inhalation that die demonstrate significant cardiac pathology. However, a gap exists in the understanding of Cl2-induced cardiac dysfunction. This study was performed to characterize cardiac dysfunction occurring after Cl2 exposure in rats at concentrations mimicking accidental human exposures (in the range of 500 or 600 ppm for 30 min). Inhalation of 500 ppm Cl2 for 30 min resulted in increased lactate in the coronary sinus of the rats suggesting an increase in anaerobic metabolism by the heart. There was also an attenuation of myocardial contractile force in an ex vivo (Langendorff technique) retrograde perfused heart preparation. After 20 h of return to room air, Cl2 exposure at 500 ppm was associated with a reduction in systolic and diastolic blood pressure as well echocardiographic/Doppler evidence of significant left ventricular systolic and diastolic dysfunction. Cl2 exposure at 600 ppm (30 min) was associated with biventricular failure (observed at 2 h after exposure) and death. Cardiac mechanical dysfunction persisted despite increasing the inspired oxygen fraction concentration in Cl2-exposed rats (500 ppm) to ameliorate hypoxia that occurs after Cl2 inhalation. Similarly ex vivo cardiac mechanical dysfunction was reproduced by sole exposure to chloramine (a potential circulating Cl2 reactant product). These results suggest an independent and distinctive role of Cl2 (and its reactants) in inducing cardiac toxicity and potentially contributing to mortality.

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“…Primary cultured mature oligodendrocytes identified as MBP-expressing cells were used in these studies. Calcium imaging was performed as previously described (57). Mature oligodendrocytes on coverslips were loaded with the calcium-sensitive Fura-2 dye by exposing cells to the standard artificial CSF (aCSF; 140 mM NaCl, 5 mM KCl, 1.5 mM CaCl 2 , 1.5 mM MgCl 2 , 10 mM Hepes, and NaOH to pH 7.4 at 37°C) containing 5 to 10 M of the cell-permeant Fura-2 AM and 0.01% of the dispersing agent Pluronic F-127 (Invitrogen, Molecular Probes, Grand Island, NY) for 15 to 40 min at 37°C.…”

Section: Primary Cultures and Calcium Imaging Of Mature Oligodendrocytesmentioning

confidence: 99%

Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation

et al. 2020

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Glutamate dysregulation occurs in multiple sclerosis (MS), but whether excitotoxic mechanisms in mature oligodendrocytes contribute to demyelination and axonal injury is unexplored. Although current treatments modulate the immune system, long-term disability ensues, highlighting the need for neuroprotection. Glutamate is elevated before T2-visible white matter lesions appear in MS. We previously reported that myelin-reactive T cells provoke microglia to release glutamate from the system xc− transporter promoting myelin degradation in experimental autoimmune encephalomyelitis (EAE). Here, we explore the target for glutamate in mature oligodendrocytes. Most glutamate-stimulated calcium influx into oligodendrocyte somas is AMPA receptor (AMPAR)–mediated, and genetic deletion of AMPAR subunit GluA4 decreased intracellular calcium responses. Inducible deletion of GluA4 on mature oligodendrocytes attenuated EAE and loss of myelinated axons was selectively reduced compared to unmyelinated axons. These data link AMPAR signaling in mature oligodendrocytes to the pathophysiology of myelinated axons, demonstrating glutamate regulation as a potential neuroprotective strategy in MS.

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Activation of gadolinium-sensitive ion channels in cardiomyocytes in early adaptive stages of volume overload-induced heart failure

Abstract: A basally-active, Gd(3+)- and GsMTx-4-sensitive SAC current that is non-selective for Na(+) and K(+), but impermeable to Ca(2+) under resting conditions is transiently elevated in LV myocytes from rats in early stages of volume overload-induced HF.

Cited by 8 publications

References 28 publications

Phosphatidylinositol 4,5-bisphosphate (PIP ₂ ) stimulates the electrogenic Na/HCO ₃ cotransporter NBCe1-A expressed in Xenopus oocytes

Phosphatidylinositol 4,5-bisphosphate (PIP ₂ ) stimulates the electrogenic Na/HCO ₃ cotransporter NBCe1-A expressed in Xenopus oocytes

Chlorine inhalation-induced myocardial depression and failure

Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation

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Activation of gadolinium-sensitive ion channels in cardiomyocytes in early adaptive stages of volume overload-induced heart failure

Abstract: A basally-active, Gd(3+)- and GsMTx-4-sensitive SAC current that is non-selective for Na(+) and K(+), but impermeable to Ca(2+) under resting conditions is transiently elevated in LV myocytes from rats in early stages of volume overload-induced HF.

Cited by 8 publications

References 28 publications

Phosphatidylinositol 4,5-bisphosphate (PIP 2 ) stimulates the electrogenic Na/HCO 3 cotransporter NBCe1-A expressed in Xenopus oocytes

Phosphatidylinositol 4,5-bisphosphate (PIP 2 ) stimulates the electrogenic Na/HCO 3 cotransporter NBCe1-A expressed in Xenopus oocytes

Chlorine inhalation-induced myocardial depression and failure

Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation

Contact Info

Product

Resources

About

Phosphatidylinositol 4,5-bisphosphate (PIP ₂ ) stimulates the electrogenic Na/HCO ₃ cotransporter NBCe1-A expressed in Xenopus oocytes

Phosphatidylinositol 4,5-bisphosphate (PIP ₂ ) stimulates the electrogenic Na/HCO ₃ cotransporter NBCe1-A expressed in Xenopus oocytes