scholarly journals Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons

2004 ◽  
Vol 287 (6) ◽  
pp. C1493-C1526 ◽  
Author(s):  
Robert W. Putnam ◽  
Jessica A. Filosa ◽  
Nicola A. Ritucci
Keyword(s):  
Brain Stem ◽  
Neuronal Response ◽  
Taste Receptor ◽  
Cellular Mechanisms ◽  
Signaling Mechanisms ◽  
Intrapulmonary Chemoreceptors ◽  
Intracellular Ca ◽  
Different Levels ◽  
Carotid Body Glomus Cells

An increase in CO2/H+ is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K+ channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO2/H+ levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca2+, gap junctions, oxidative stress, glial cells, bicarbonate, CO2, and neurotransmitters. The normal target for these signals is generally believed to be a K+ channel, although it is likely that many K+ channels as well as Ca2+ channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO2- and/or H+-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO2/H+.

Mechanisms of membrane estrogen receptor-α-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line

2005 ◽  
Vol 288 (2) ◽  
pp. E388-E397 ◽  
Author(s):  
Nataliya N. Bulayeva ◽  
Ann L. Wozniak ◽  
L. Leanne Lash ◽  
Cheryl S. Watson
Keyword(s):  
Estrogen Receptor ◽  
Cell Line ◽  
Estrogen Receptor Α ◽  
Signaling Mechanism ◽  
Signaling Mechanisms ◽  
Intracellular Ca ◽  
A Cell ◽  
17Β Estradiol ◽  
Rapid Stimulation

The role of membrane estrogen receptor-α (mERα) in rapid nongenomic responses to 17β-estradiol (E2) was tested in sublines of GH3/B6 rat prolactinoma cells selected for high (GH3/B6/F10) and low (GH3/B6/D9) mERα expression. E2 elicited rapid, concentration-dependent intracellular Ca2+ concentration ([Ca2+]i) increases in the F10 subline. Lack of inhibition by thapsigargin depletion of intracellular Ca2+ pools, together with abrogation of the response in Ca2+-free medium, suggested an extracellular source of Ca2+ for this response. The participation of voltage-dependant channels in the E2-induced [Ca2+]i increase was confirmed by the specific L-type Ca2+ channel inhibitor nifedipine. For comparison, the D9 mERα-depleted subline was insensitive to steroid action via this signaling mechanism. [Ca2+]i elevation was correlated with prolactin (PRL) release in the F10 cell line in as little as 3 min. E2 caused a much higher PRL release than KCl treatment (which caused maximal Ca2+ elevation), suggesting that secretion was also controlled by additional mechanisms. Participation of mERα in these effects was confirmed by the ability of E2-peroxidase (a cell-impermeable analog of E2) to cause these responses, blockage of the responses with the ER antagonist ICI 182 780, and the inability of the E2 stereoisomer 17α-E2 to elicit a response. Thus rapid exocytosis of PRL is regulated in these cells by mERα signaling to specific Ca2+ channels utilizing extracellular Ca2+ sources and additional signaling mechanisms.

Spontaneous transient depolarizations in lymphatic vessels of the guinea pig mesentery: pharmacology and implication for spontaneous contractility

2008 ◽  
Vol 295 (5) ◽  
pp. H1989-H2000 ◽  
Author(s):  
Pierre-Yves von der Weid ◽  
Mozibur Rahman ◽  
Mohammad S. Imtiaz ◽  
Dirk F. van Helden
Keyword(s):  
Guinea Pig ◽  
Ryanodine Receptors ◽  
Lymphatic Vessels ◽  
Channel Blockers ◽  
Pharmacological Agents ◽  
Agonist Stimulation ◽  
Signaling Mechanisms ◽  
Intracellular Ca ◽  
Intracellular Microelectrodes

Guinea pig mesenteric lymphatic vessels exhibit rhythmic constrictions induced by action potential (AP)-like spikes and initiated by entrainment of spontaneous transient depolarizations (STDs). To characterize STDs and the signaling mechanisms responsible for their occurrence, we used intracellular microelectrodes, Ca2+ imaging, and pharmacological agents. In our investigation of the role of intracellular Ca2+ released from Ca2+ stores, we observed that intracellular Ca2+ transients accompanied some STDs, although there were many exceptions where Ca2+ transients occurred without accompanying STDs. STD frequency and amplitude were markedly affected by activators/inhibitors of inositol 1,4,5-trisphosphate receptors (IP3Rs) but not by treatments known to alter Ca2+ release via ryanodine receptors. A role for Ca2+-activated Cl− (ClCa) channels was indicated, as STDs were dependent on the Cl− but not Na+ concentration of the superfusing solution and were inhibited by the ClCa channel blockers niflumic acid (NFA), anthracene 9-carboxylic acid, and 5-nitro-2-(3-phenylpropylamino)benzoic acid but not by the volume-regulated Cl− blocker DIDS. Increases in STD frequency and amplitude induced by agonist stimulation were also inhibited by NFA. Nifedipine, the hyperpolarization-activated inward current blocker ZD-7288, and the nonselective cation/store-operated channel blockers SKF-96365, Gd3+, and Ni2+ had no or marginal effects on STD activity. However, nifedipine, 2-aminoethoxydiphenyl borate, NFA, SKF-96365, Gd3+, and Ni2+ altered the occurrence of spontaneous APs. Our findings support a role for Ca2+ release through IP3Rs and a resultant opening of ClCa channels in STD generation and confirm the importance of these events in the initiation of lymphatic spontaneous APs and subsequent contractions. The abolition of spontaneous APs by blockers of other excitatory ion channels suggests a contribution of these conductances to lymphatic pacemaking.

Genesis and Regulation of the Heart Automaticity

2008 ◽  
Vol 88 (3) ◽  
pp. 919-982 ◽  
Author(s):  
Matteo E. Mangoni ◽  
Joël Nargeot
Keyword(s):  
Ion Channels ◽  
Current Knowledge ◽  
Genetically Engineered ◽  
Cardiac Cells ◽  
Mouse Strains ◽  
Cellular Mechanisms ◽  
Cardiac Pacemaking ◽  
Intracellular Ca ◽  
Cardiac Automaticity

The heart automaticity is a fundamental physiological function in higher organisms. The spontaneous activity is initiated by specialized populations of cardiac cells generating periodical electrical oscillations. The exact cascade of steps initiating the pacemaker cycle in automatic cells has not yet been entirely elucidated. Nevertheless, ion channels and intracellular Ca2+ signaling are necessary for the proper setting of the pacemaker mechanism. Here, we review the current knowledge on the cellular mechanisms underlying the generation and regulation of cardiac automaticity. We discuss evidence on the functional role of different families of ion channels in cardiac pacemaking and review recent results obtained on genetically engineered mouse strains displaying dysfunction in heart automaticity. Beside ion channels, intracellular Ca2+ release has been indicated as an important mechanism for promoting automaticity at rest as well as for acceleration of the heart rate under sympathetic nerve input. The potential links between the activity of ion channels and Ca2+ release will be discussed with the aim to propose an integrated framework of the mechanism of automaticity.

scholarly journals Role of impaired endothelial cell Ca2+ signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy

2013 ◽  
Vol 304 (7) ◽  
pp. H935-H945 ◽  
Author(s):  
Natalia I. Gokina ◽  
Adrian D. Bonev ◽  
Alexander P. Gokin ◽  
Gabriela Goloman
Keyword(s):  
Endothelial Cell ◽  
Vascular Dysfunction ◽  
Maternal Blood ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Cellular Mechanisms ◽  
Citrate Buffer ◽  
Pregnant Rats ◽  
Intracellular Ca

Diabetes mellitus in pregnancy is associated with impaired endothelium-mediated dilatation of maternal arteries, although the underlying cellular mechanisms remain unknown. In this study, we hypothesized that diabetes during rat gestation attenuates agonist-induced uterine vasodilation through reduced endothelial cell (EC) Ca2+ elevations and impaired smooth muscle cell (SMC) hyperpolarization and SMC intracellular Ca2+ concentration ([Ca2+]i) responses. Diabetes was induced by an injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with a citrate buffer. Fura-2-based measurements of SMC [Ca2+]i or microelectrode recordings of SMC membrane potential were performed concurrently with dilator responses to ACh in uteroplacental arteries from control and diabetic pregnant rats. Basal levels of EC [Ca2+]i and ACh-induced EC [Ca2+]i elevations in pressurized vessels and small EC sheets were studied as well. Diabetes reduced ACh-induced vasodilation due to a markedly impaired EDHF-mediated response. Diminished vasodilation to ACh was associated with attenuated SMC hyperpolarization and [Ca2+]i responses. Basal levels of EC [Ca2+]i and ACh-induced EC [Ca2+]i elevations were significantly reduced by diabetes. In conclusion, these data demonstrate that reduced endothelium-mediated hyperpolarization contributes to attenuated uteroplacental vasodilation and SMC [Ca2+]i responses to ACh in diabetic pregnancy. Impaired endothelial Ca2+ signaling is in part responsible for endothelial dysfunction in the uterine resistance vasculature of diabetic rats. Pharmacological improvement of EC Ca2+ handling may provide an important strategy for the restoration of endothelial function and enhancement of maternal blood flow in human pregnancies complicated by diabetes.

Kisspeptin induction of somatolactin-α release in goldfish pituitary cells: functional role of cAMP/PKA-, PLC/PKC-, and Ca2+/calmodulin-dependent cascades

2014 ◽  
Vol 307 (10) ◽  
pp. E872-E884 ◽  
Author(s):  
Quan Jiang ◽  
Mulan He ◽  
Wendy K. W. Ko ◽  
Anderson O. L. Wong
Keyword(s):  
Protein Kinase ◽  
Functional Role ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Signaling Mechanisms ◽  
Intracellular Ca ◽  
Subsequent Activation

Although the importance of kisspeptin in the pituitary is firmly established, the signaling mechanisms for the pituitary actions of kisspeptin are still largely unknown. Somatolactin (SL), a member of the growth hormone (GH)/prolactin (PRL) family, is a pituitary hormone with pleiotropic functions in fish, but its regulation by kisspeptin has not been examined. To investigate the functional role of kisspeptin in SL regulation, expression of two paralogues of goldfish Kiss1 receptors (Kiss1ra and Kiss1rb) were confirmed in immunoidentified SLα but not SLβ cells isolated by RT-PCR coupled with laser capture microdissection. In goldfish pituitary cells prepared from neurointermediate lobe (NIL), synthetic goldfish Kiss decapeptides (gKiss1-10 and gKiss2-10) could increase SLα release. Consistent with the lack of Kiss1r expression in SLβ cells, SLβ release was not altered by kisspeptin stimulation. In parallel experiments, goldfish gKiss1-10 could elevate cyclic adenosine monophosphate (cAMP) production, upregulate protein kinase A (PKA) and protein kinase C (PKC) activities, and trigger a rapid rise in intracellular Ca2+ levels in goldfish NIL cells. Using a pharmacological approach, cAMP/PKA and phospholipase C (PLC)/PKC pathways and subsequent activation of Ca2+/calmodulin (CaM)-dependent cascades were shown to be involved in SLα release induced by gKiss1-10. Apparently, the Ca2+-dependent cascades were triggered by extracellular Ca2+ entry via voltage-sensitive Ca2+ channels and mobilization of inositol trisphosphate-sensitive intracellular Ca2+ stores. Our results demonstrate that gKiss1-10 can act directly at the pituitary level to trigger SLα release via a complex network of post-receptor signaling mechanisms.

Abstract 279: Mitochondrial Bioenergetic Signaling Drives Myofibroblast Transdifferentiation

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Alyssa A Lombardi ◽  
Ehtesham Arif ◽  
Timothy S Luongo ◽  
John W Elrod
Keyword(s):  
Cardiac Fibrosis ◽  
Contractile Function ◽  
Glycolytic Flux ◽  
Lv Function ◽  
Cellular Mechanisms ◽  
Adult Mice ◽  
Intracellular Ca ◽  
Fibrotic Diseases ◽  
Inducible Gene

When the heart is injured, quiescent fibroblasts differentiate into contractile, synthetic myofibroblasts. Initially fibrosis is reparative, but when chronic it becomes maladaptive and contributes to HF. Intracellular Ca 2+ ( i Ca 2+ ) signaling is reported to be necessary for myofibroblast transdifferentiation yet the role of mitochondrial Ca 2+ ( m Ca 2+ ) exchange has not been explored. The Mcu gene encodes the channel-forming subunit of the m Ca 2+ uniporter channel (MCUc) and is required for acute m Ca 2+ uptake. To examine the contribution of m Ca 2+ in cardiac fibrosis, we generated conditional, fibroblast-specific knockout mice by crossbreeding Mcu fl/fl mice with Col1a2-CreERT mice (Col1a2- Mcu -/- ), permitting tamoxifen-inducible gene deletion in adult mice. Col1a2- Mcu -/- mice and controls were subjected to ligation of the left coronary artery and cardiac function was examined by echocardiography. Loss of fibroblast Mcu worsened LV function and increased fibrosis, as evaluated by Mason’s trichrome staining and qPCR analysis of fibrotic gene expression. To examine the cellular mechanisms responsible for the increased fibrosis we isolated mouse embryonic fibroblasts (MEFs) from Mcu fl/fl mice and deleted Mcu with Cre-adenovirus. When challenged with pro-fibrotic ligands (TGF-β and AngII), Mcu -/- MEFs exhibited decreased m Ca 2+ uptake and enhanced i Ca 2+ transient amplitude. Loss of Mcu promoted myofibroblast transdifferentiation: increased α-SMA expression and contractile function (gel retraction) and decreased migration and proliferation. Mcu -/- MEFs were more glycolytic with increased phosphorylation (inactivation) of pyruvate dehydrogenase. Genetic activation of glycolysis with a Pfk2 mutant in WT MEFs promoted myofibroblast differentiation. Conversely, genetic inhibition of glycolytic flux ablated the increased transdifferentiation observed in Mcu -/- MEFs. Further, TGF-β and AngII altered the expression of regulatory MCUc components in WT MEFs. Our results suggest that alterations in m Ca 2+ uptake and bioenergetic pathways are necessary for myofibroblast transdifferentiation. Thus, energetic signaling represents a novel therapeutic target to impede HF progression and other progressive fibrotic diseases.

scholarly journals Nasal Solitary Chemoreceptor Cell Responses to Bitter and Trigeminal Stimulants In Vitro

2008 ◽  
Vol 99 (6) ◽  
pp. 2929-2937 ◽  
Author(s):  
Brian D. Gulbransen ◽  
Tod R. Clapp ◽  
Thomas E. Finger ◽  
Sue C. Kinnamon
Keyword(s):  
Fluorescent Protein ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Receptor Ligands ◽  
Isolated Cells ◽  
Taste System ◽  
Intracellular Ca ◽  
Green Fluorescent

Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear. Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein α-gustducin, PLCβ2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants. SCCs from the anterior nasal cavity were isolated from transgenic mice in which green fluorescent protein (GFP) expression was driven by either TRPM5 or gustducin. Isolated cells were exposed to a variety of test stimuli to determine which substances caused an increase in intracellular Ca2+ ([Ca2+]i). GFP-positive cells respond with increased [Ca2+]i to the bitter receptor ligand denatonium and this response is blocked by the PLC inhibitor U73122. In addition, GFP+ cells respond to the neuromodulators adenosine 5′-triphosphate and acetylcholine but only very rarely to other bitter-tasting or trigeminal stimuli. Our results demonstrate that TRPM5- and gustducin-expressing nasal SCCs respond to the T2R agonist denatonium via a PLC-coupled transduction cascade typical of T2Rs in the taste system.

Value-driven issues throughout the development of sociological theory

2020 ◽  
pp. 147-160
Author(s):  
Gulbarshyn Chepurko ◽  
Valerii Pylypenko
Keyword(s):  
Social Interactions ◽  
Social System ◽  
Sociological Theory ◽  
Social Scientists ◽  
Social Sphere ◽  
Technological Advances ◽  
The Social ◽  
The Individual ◽  
Different Levels

The paper examines and compares how the major sociological theories treat axiological issues. Value-driven topics are analysed in view of their relevance to society in times of crisis, when both societal life and the very structure of society undergo dramatic change. Nowadays, social scientists around the world are also witnessing such a change due to the emergence of alternative schools of sociological thought (non-classical, interpretive, postmodern, etc.) and, subsequently, the necessity to revise the paradigms that have been existed in sociology so far. Since the above-mentioned approaches are often used to address value-related issues, building a solid theoretical framework for these studies takes on considerable significance. Furthermore, the paradigm revision has been prompted by technological advances changing all areas of people’s lives, especially social interactions. The global human community, integral in nature, is being formed, and production of human values now matters more than production of things; hence the “expansion” of value-focused perspectives in contemporary sociology. The authors give special attention to collectivities which are higher-order units of the social system. These units are described as well-organised action systems where each individual performs his/her specific role. Just as the role of an individual is distinct from that of the collectivity (because the individual and the collectivity are different as units), so too a distinction is drawn between the value and the norm — because they represent different levels of social relationships. Values are the main connecting element between the society’s cultural system and the social sphere while norms, for the most part, belong to the social system. Values serve primarily to maintain the pattern according to which the society is functioning at a given time; norms are essential to social integration. Apart from being the means of regulating social processes and relationships, norms embody the “principles” that can be applied beyond a particular social system. The authors underline that it is important for Ukrainian sociology to keep abreast of the latest developments in the field of axiology and make good use of those ideas because this is a prerequisite for its successful integration into the global sociological community.

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