scholarly journals Volume-dependent taurine release from cultured astrocytes requires permissive [Ca2+]iand calmodulin

1999 ◽  
Vol 277 (4) ◽  
pp. C823-C832 ◽  
Author(s):  
Alexander A. Mongin ◽  
Zhaohui Cai ◽  
Harold K. Kimelberg
Keyword(s):  
Cell Swelling ◽  
Transport Systems ◽  
Channel Blockers ◽  
Organic Osmolytes ◽  
Taurine Release ◽  
Cultured Astrocytes ◽  
High K ◽  
Intracellular Ca ◽  
Free Media ◽  
Taurine Efflux

Cell swelling results in regulatory activation of multiple conductive anion pathways permeable toward a broad spectrum of intracellular organic osmolytes. Here, we explore the involvement of extracellular and intracellular Ca2+ in volume-dependent [3H]taurine efflux from primary cultured astrocytes and compare the Ca2+ sensitivity of this efflux in slow (high K+ medium induced) and fast (hyposmotic medium induced) cell swelling. Neither Ca2+-free medium nor Ca2+-channel blockers prevented the volume-dependent [3H]taurine release. In contrast, loading cells with the membrane-permeable Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA)-AM suppressed [3H]taurine efflux by 65–70% and 25–30% under high-K+ and hyposmotic conditions, respectively. Fura 2 measurements confirmed that BAPTA-AM, but not Ca2+-free media, significantly reduced resting intracellular Ca2+concentration ([Ca2+]i). The calmodulin antagonists trifluoperazine and fluphenazine reversibly and irreversibly, respectively, inhibited the high-K+-induced [3H]taurine release, consistent with their known actions on calmodulin. In hyposmotic conditions, the effects were less pronounced. These data suggest that volume-dependent taurine release requires minimal basal [Ca2+]iand involves calmodulin-dependent step(s). Quantitative differences in Ca2+/calmodulin sensitivity of high-K+-induced and hyposmotic medium-induced taurine efflux are due to both the effects of the inhibitors on high-K+-induced cell swelling and their effects on transport systems and/or signaling mechanisms determining taurine efflux.

The volume-sensitive organic osmolyte-anion channel VSOAC is regulated by nonhydrolytic ATP binding

1994 ◽  
Vol 267 (5) ◽  
pp. C1203-C1209 ◽  
Author(s):  
P. S. Jackson ◽  
R. Morrison ◽  
K. Strange
Keyword(s):  
Ketone Bodies ◽  
Anion Channel ◽  
Metabolic Inhibitors ◽  
Cell Swelling ◽  
Organic Osmolytes ◽  
Pipette Solution ◽  
Organic Osmolyte ◽  
Atp Levels ◽  
Patch Pipette ◽  
Taurine Efflux

Efflux of intracellular organic osmolytes to the external medium is a ubiquitous response to cell swelling. Accumulating evidence indicates that volume regulatory loss of structurally unrelated organic osmolytes from cells is mediated by a relatively nonselective volume-sensitive anion channel. In C6 cells, we have termed this channel VSOAC for volume-sensitive organic osmolyte-anion channel. Swelling-induced activation of VSOAC required the presence of ATP or nonhydrolyzable ATP analogues [adenosine 5'-O-(3-thiotriphosphate), adenylylmethyl-enediphosphonate (AMP-PCP), or 5'-adenylylimidodiphosphate] in the patch pipette. Sustained activation of VSOAC also required ATP. Channel rundown was observed when cellular ATP levels were lowered by intracellular dialysis with the patch pipette solution. Rundown was prevented by the ATP analogue AMP-PCP. Passive swelling-induced myo-[3H]inositol and [3H]taurine efflux was blocked by metabolic inhibitors that decreased cellular ATP levels. Titration of cellular ATP levels with azide demonstrated that the apparent dissociation constant (Kd) for ATP of both myo-inositol and taurine efflux was approximately 1.7 mM. The high Kd for ATP indicates that cellular metabolic state plays an important role in modulating organic osmolyte loss. Regulation of VSOAC activity by ATP prevents depletion of metabolically expensive organic osmolytes when cellular energy production is reduced. In addition, ATP-dependent regulation provides essential feedback to minimize the loss of energy-producing carbon sources such as pyruvate, short-chain fatty acids, ketone bodies, and amino acids, which readily permeate this channel.

Dihydropyridine-sensitive cell volume regulation in proximal tubule: the calcium window

1990 ◽  
Vol 259 (6) ◽  
pp. F950-F960 ◽  
Author(s):  
N. A. McCarty ◽  
R. G. O'Neil
Keyword(s):  
Cell Volume ◽  
Volume Regulation ◽  
Regulatory Volume Decrease ◽  
Cell Volume Regulation ◽  
Cell Swelling ◽  
Channel Blockers ◽  
Ca Channel ◽  
Hypotonic Solution ◽  
Dependent Manner ◽  
Intracellular Ca

The mechanism underlying the activation of hypotonic cell volume regulation was studied in rabbit proximal straight tubule (PST). When isolated non-perfused tubules were exposed to hypotonic solution, cells swelled rapidly and then underwent a regulatory volume decrease (RVD). The extent of regulation after swelling was highly dependent on extracellular Ca concentration ([Ca2+]o), with a half-maximal inhibition (K1/2) for [Ca2+]o of approximately 100 microM. RVD was blocked by the Ca-channel blockers verapamil, lanthanum, and the dihydropyridines (DHP) nifedipine and nitrendipine, implicating voltage-activated Ca channels in the RVD response. Using the fura-2 fluorescence-ratio technique, we observed that cell swelling caused a sustained rise in intracellular Ca ([Ca2+]i) only when [Ca2+]o was normal (1 mM) but not when [Ca2+]o was low (1-10 microM). Furthermore, external Ca was required early on during swelling to induce RVD. If RVD was initially blocked by reducing [Ca2+]o or by addition of verapamil during hypotonic swelling, volume regulation could only be restored by subsequently inducing Ca entry within the first 1 min or less of exposure to hypotonic solution. These data indicate a "calcium window" of less than 1 min, during which RVD is sensitive to Ca, and that part of the Ca-dependent mechanism responsible for achieving RVD undergoes inactivation after swelling. It is concluded that RVD in rabbit PST is modulated by Ca via a DHP-sensitive mechanism in a time-dependent manner.

scholarly journals TRPV4 channels contribute to renal myogenic autoregulation in neonatal pigs

2017 ◽  
Vol 313 (5) ◽  
pp. F1136-F1148 ◽  
Author(s):  
Hitesh Soni ◽  
Dieniffer Peixoto-Neves ◽  
Anberitha T. Matthews ◽  
Adebowale Adebiyi
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cell Swelling ◽  
Transient Receptor Potential Vanilloid ◽  
Channel Blockers ◽  
Renal Autoregulation ◽  
Neonatal Pigs ◽  
Intracellular Ca ◽  
Neonatal Pig ◽  
Transient Receptor

Myogenic response, a phenomenon in which resistance size arteries and arterioles swiftly constrict or dilate in response to an acute elevation or reduction, respectively, in intravascular pressure is a key component of renal autoregulation mechanisms. Although it is well established that the renal system is functionally immature in neonates, mechanisms that regulate neonatal renal blood flow (RBF) remain poorly understood. In this study, we investigated the hypothesis that members of the transient receptor potential vanilloid (TRPV) channels are molecular components of renal myogenic constriction in newborns. We show that unlike TRPV1–3, TRPV4 channels are predominantly expressed in neonatal pig preglomerular vascular smooth muscle cells (SMCs). Intracellular Ca2+ concentration ([Ca2+]i) elevation induced by osmotic cell swelling was attenuated by TRPV4, L-type Ca2+, and stretch-activated Ca2+ channel blockers but not phospholipase A2 inhibitor. Blockade of TRPV4 channels reversed steady-state myogenic tone and inhibited pressure-induced membrane depolarization, [Ca2+]i elevation, and constriction in distal interlobular arteries. A step increase in arterial pressure induced efficient autoregulation of renal cortical perfusion and total RBF in anesthetized and mechanically ventilated neonatal pigs. Moreover, intrarenal arterial infusion of the TRPV4 channel blockers HC 067047 and RN 1734 attenuated renal autoregulation in the pigs. These data suggest that renal myogenic autoregulation is functional in neonates. Our findings also indicate that TRPV4 channels are mechanosensors in neonatal pig preglomerular vascular SMCs and contribute to renal myogenic autoregulation.

Taurine transport in skate hepatocytes. II. Volume activation, energy, and sulfhydryl dependence

1992 ◽  
Vol 262 (3) ◽  
pp. G451-G460 ◽  
Author(s):  
N. Ballatori ◽  
J. L. Boyer
Keyword(s):  
Plasma Membrane ◽  
Concentration Gradient ◽  
Regulatory Volume Decrease ◽  
Metabolic Inhibitors ◽  
Cell Swelling ◽  
Disulfonic Acid ◽  
Organic Osmolytes ◽  
Taurine Transport ◽  
Taurine Concentration ◽  
Taurine Efflux

Isolated skate (Raja erinacea) hepatocytes swollen in hypotonic media exhibited a regulatory volume decrease (RVD) that was associated with only a small increase in K+ or 86Rb+ efflux but a substantial increase in the release of taurine, an amino acid found in high concentrations in skate hepatocytes. Taurine efflux was stimulated in media made hypotonic by addition of H2O or removal of NaCl, as well as in cells swollen in isotonic media containing rapidly penetrating solutes (202 mM ethylene glycol or 202 mM additional urea substituted for 101 mM NaCl), suggesting that cell swelling rather than hyposmolarity is the stimulus for the activation of taurine release. In contrast, release of glutathione, L-[14C]alanine and other alpha-amino acids (e.g., threonine, serine, glutamate, glutamine, glycine, or valine) was unaffected by dilution with 40% H2O. Taurine efflux was not altered by replacement of extracellular Na+ with choline+ or K+ and was only slightly diminished by replacing Cl- with NO3-. Addition of 50 mM taurine or hypotaurine to the incubation media also had no effect on volume-stimulated [14C]taurine efflux, suggesting that the taurine concentration gradient across the plasma membrane is not the driving force. Volume-stimulated taurine transport was temperature sensitive, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibitable (0.5 mM), and nearly completely blocked by metabolic inhibitors (2,4-dinitrophenol, KCN, sodium azide, oligomycin, carbonyl cyanide m-chlorophenylhydrazone, and antimycin A), suggesting an active energy-dependent process. Sulfhydryl-reactive reagents (N-ethylmaleimide, diamide, iodoacetate, tert-butyl hydroperoxide, and mercury) also blocked volume-stimulated taurine efflux, whereas efflux was unaffected by Ca2+ ionophore, phorbol ester, dibutyryl-adenosine 3',5'-cyclic monophosphate, vasopressin, or pretreatment with ouabain or furosemide. N-ethylmaleimide, diamide, 2,4-dinitrophenol, and iodoacetate plus KCN also inhibited the RVD. These findings suggest that, in contrast to hepatocytes from most vertebrate species, RVD in skate hepatocytes is associated with the release of only a small fraction of intracellular K+ but a substantial fraction of intracellular taurine and perhaps other organic osmolytes. This volume-activated taurine transport mechanism is energy and sulfhydryl group dependent and is not related to the taurine concentration gradient across the skate hepatocyte plasma membrane.

Volume-sensitive anion channels mediate swelling-activated inositol and taurine efflux

1993 ◽  
Vol 265 (6) ◽  
pp. C1489-C1500 ◽  
Author(s):  
P. S. Jackson ◽  
K. Strange
Keyword(s):  
Fatty Acids ◽  
Anion Channel ◽  
Anion Transport ◽  
Cell Swelling ◽  
C6 Glioma Cells ◽  
Organic Osmolytes ◽  
Transport Pathway ◽  
Whole Cell ◽  
Efflux Mechanism ◽  
Taurine Efflux

C6 glioma cells accumulate the organic osmolyte inositol in response to chronic hypertonic stress. Upon return to isotonic conditions, cell swelling activates a Na(+)-independent passive low-affinity inositol efflux mechanism that is inhibited 80-100% by a number of anion transport blockers, certain lipoxygenase blockers, and various polyunsaturated fatty acids. Taurine efflux is also enhanced by cell swelling. The taurine efflux pathway has characteristics that are identical to those of the inositol efflux mechanism, including kinetics of activation and inactivation, osmotic sensitivity, pharmacological sensitivity, and inhibition by certain Na+ and Cl- substitutes. These results suggest strongly that volume-sensitive inositol and taurine efflux are mediated by a common transport mechanism. The inhibition of the transport pathway by anion transport blockers and unsaturated fatty acids suggests indirectly that efflux of these solutes may be mediated by an anion channel. Whole cell patch clamp measurements in CsCl solutions were used to test this hypothesis. Under hypertonic conditions, C6 cells had an extremely low membrane conductance (approximately 0.02 nS/pF). After cell swelling, however, whole cell anion conductance was activated rapidly to values up to 1.5-2 nS/pF. This conductance was outwardly rectified and selective for anions and was inhibited 80-100% by blockers of swelling-activated inositol and taurine efflux. The relative taurine permeability (i.e., Ptaurine/PCl) of the conductance was 0.20. Isosmotic replacement of raffinose in the external medium with inositol or sorbitol induced a transient inward current, suggesting that Cl- and these polyols compete for common binding sites on the channel. We conclude that a volume-sensitive anion channel mediates the efflux of structurally diverse organic osmolytes such as taurine and inositol from the cell.

scholarly journals Properties of Taurine Release in Glucose-Free Media in Hippocampal Slices from Developing and Adult Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Simo S. Oja ◽  
Pirjo Saransaari
Keyword(s):  
Excitatory Amino Acid ◽  
Hippocampal Slices ◽  
Anion Channel ◽  
Channel Blockers ◽  
Taurine Release ◽  
Amino Acid Receptors ◽  
Adult Mice ◽  
Superfusion System ◽  
Free Media ◽  
Old Mice

The release of preloaded [3H]taurine from hippocampal slices from developing 7-day-old and young adult 3-month-old mice was studied in a superfusion system in the absence of glucose. These hypoglycemic conditions enhanced the release at both ages, the effect being markedly greater in developing mice. A depolarizing K+ concentration accentuated the release, which indicates that it was partially mediated by exocytosis. The anion channel blockers were inhibitory, witnessing the contribution of ion channels. NO-generating agents fomented the release as a sign of the participation of excitatory amino acid receptors. The other second messenger systems were apparently less efficient. The much greater taurine release could be a reason for the well-known greater tolerance of developing nervous tissue to lack of glucose.

ATP regulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca2+-sensitive mechanisms

2005 ◽  
Vol 288 (1) ◽  
pp. C204-C213 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Intracellular Signaling ◽  
Anion Channel ◽  
Cell Swelling ◽  
Organic Osmolytes ◽  
Signaling Mechanism ◽  
Pharmacological Agents ◽  
Organic Osmolyte ◽  
Primary Astrocyte ◽  
Intracellular Ca ◽  
Rat Astrocytes

Ubiquitously expressed volume-regulated anion channels (VRACs) are activated in response to cell swelling but may also show limited activity in nonswollen cells. VRACs are permeable to inorganic anions and small organic osmolytes, including the amino acids aspartate, glutamate, and taurine. Several recent reports have demonstrated that neurotransmitters or hormones, such as ATP and vasopressin, induce or strongly potentiate astrocytic whole cell Cl− currents and amino acid release, which are inhibited by VRAC blockers. In the present study, we explored the intracellular signaling mechanisms mediating the effects of ATP on d-[3H]aspartate release via the putative VRAC pathway in rat primary astrocyte cultures. Cells were exposed to moderate (5%) or substantial (30%) reductions in medium osmolarity. ATP strongly potentiated d-[3H]aspartate release in both moderately swollen and substantially swollen cells. These ATP effects were blocked (≥80% inhibition) by intracellular Ca2+ chelation with BAPTA-AM, calmodulin inhibitors, or a combination of the inhibitors of protein kinase C (PKC) and calmodulin-dependent kinase II (CaMK II). In contrast, control d-[3H]aspartate release activated by the substantial hyposmotic swelling showed little (≤25% inhibition) sensitivity to the same pharmacological agents. These data indicate that ATP regulates VRAC activity via two separate Ca2+-sensitive signaling cascades involving PKC and CaMK II and that cell swelling per se activates VRACs via a separate Ca2+/calmodulin-independent signaling mechanism. Ca2+-dependent organic osmolyte release via VRACs may contribute to the physiological functions of these channels in the brain, including astrocyte-to-neuron intercellular communication.

scholarly journals Inhibition of Brain Swelling after Ischemia-Reperfusion byβ-Adrenergic Antagonists: Correlation with Increased K+and Decreased Ca2+Concentrations in Extracellular Fluid

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Dan Song ◽  
Junnan Xu ◽  
Ting Du ◽  
Enzhi Yan ◽  
Leif Hertz ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Extracellular Fluid ◽  
Artery Occlusion ◽  
Cell Swelling ◽  
Cultured Astrocytes ◽  
High K ◽  
Ionic Changes ◽  
Adrenergic Antagonists ◽  
Cerebral Artery Occlusion ◽  
Adrenergic Activation

Infarct size and brain edema following ischemia/reperfusion are reduced by inhibitors of the Na+, K+, 2Cl−, and water cotransporter NKCC1 and byβ1-adrenoceptor antagonists. NKCC1 is a secondary active transporter, mainly localized in astrocytes, driven by transmembrane Na+/K+gradients generated by the Na+,K+-ATPase. The astrocytic Na+,K+-ATPase is stimulated by small increases in extracellular K+concentration and by theβ-adrenergic agonist isoproterenol. Larger K+increases, as occurring during ischemia, also stimulate NKCC1, creating cell swelling. This study showed no edema after 3 hr medial cerebral artery occlusion but pronounced edema after 8 hr reperfusion. The edema was abolished by inhibitors of specificallyβ1-adrenergic pathways, indicating failure of K+-mediated, but notβ1-adrenoceptor-mediated, stimulation of Na+,K+-ATPase/NKCC1 transport during reoxygenation. Ninety percent reduction of extracellular Ca2+concentration occurs in ischemia. Ca2+omission abolished K+uptake in normoxic cultures of astrocytes after addition of 5 mM KCl. A large decrease in ouabain potency on K+uptake in cultured astrocytes was also demonstrated in Ca2+-depleted media, and endogenous ouabains are needed for astrocytic K+uptake. Thus, among the ionic changes induced by ischemia, the decrease in extracellular Ca2+causes failure of the high-K+-stimulated Na+,K+-ATPase/NKCC1 ion/water uptake, makingβ1-adrenergic activation the only stimulus and its inhibition effective against edema.

Reactive oxygen species are important mediators of taurine release from skeletal muscle cells

2003 ◽  
Vol 284 (6) ◽  
pp. C1362-C1373 ◽  
Author(s):  
Niels Ørtenblad ◽  
Jette Feveile Young ◽  
Niels Oksbjerg ◽  
Jacob Holm Nielsen ◽  
Ian Henry Lambert
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Reactive Oxygen ◽  
Anion Channel ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Cell Swelling ◽  
Oxygen Species ◽  
Taurine Release ◽  
Taurine Efflux

The present study illustrates elements of the signal cascades involved in the activation of taurine efflux pathways in myotubes derived from skeletal muscle cells. Exposing primary skeletal muscle cells, loaded with 14C-taurine, to 1) hypotonic media, 2) the phospholipase A2 (PLA2) activator melittin, 3) anoxia, or 4) lysophosphatidyl choline (LPC) causes an increase in 14C-taurine release and a concomitant production of reactive oxygen species (ROS). The antioxidants butulated hydroxy toluene and vitamin E inhibit the taurine efflux after cell swelling, anoxia, and addition of LPC. The muscle cells possess two separate taurine efflux pathways, i.e., a swelling- and melittin-induced pathway that requires 5-lipoxygenase activity for activation and a LPC-induced pathway. The two pathways are distinguished by their opposing sensitivity toward the anion channel blocker DIDS and cholesterol. These data provide evidence for PLA2 products and ROS as key mediators of the signal cascade leading to taurine efflux in muscle.

Volume-sensitive taurine efflux from mammary tissue is not obliged to utilize volume-activated anion channels

1996 ◽  
Vol 16 (6) ◽  
pp. 459-465 ◽  
Author(s):  
D. B. Shennan ◽  
M. J. Cliff ◽  
P. Hawkins
Keyword(s):  
Anion Transport ◽  
Cell Swelling ◽  
Mammary Tissue ◽  
Anion Channels ◽  
Taurine Release ◽  
Amino Acid Transport System ◽  
Transport Inhibitors ◽  
Swelling Volume ◽  
Taurine Efflux ◽  
Stimulation Of

Cell-swelling, induced by a hyposmotic shock, activates the release of taurine from lactating rat mammary tissue expiants. The degree of stimulation of taurine efflux was dependent upon the extent of cell-swelling. Volume-sensitive taurine release was attenuated by the anion transport inhibitors NPPB, DIOA, DIDS, niflumate, flufenamate, mefenamate and diiodosalicylate but not by salicylate. Cell-swelling, following a hyposmotic challenge, did not increase the unidirectional efflux of radiolabelled I− or D-asparate from mammary tissue expiants. The results suggest that although mammary tissue expresses a volume-sensitive amino acid transport system which is inhibited by anion transport blockers the pathway has no identity with volume-activated anion channels.

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