scholarly journals Excitatory GABA: How a Correct Observation May Turn Out to be an Experimental Artifact

2012 ◽  
Vol 3 ◽  
Author(s):  
Piotr Bregestovski ◽  
Christophe Bernard
Keyword(s):  
Experimental Artifact ◽  
Excitatory Gaba

The heart works against gravity

1993 ◽  
Vol 265 (4) ◽  
pp. R715-R720 ◽  
Author(s):  
R. S. Seymour ◽  
A. R. Hargens ◽  
T. J. Pedley
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Potential Energy ◽  
Flow Rate ◽  
Viscous Resistance ◽  
Arterial Blood ◽  
Experimental Artifact ◽  
Continuous Stream ◽  
Laboratory Models ◽  
Poiseuille Equation

The circulatory systems of vertebrate animals are closed, and blood leaves and returns to the heart at the same level. It is often concluded, therefore, that the heart works only against the viscous resistance of the system, not against gravity, even in vascular loops above the heart in which the siphon principle operates. However, we argue that the siphon principle does not assist blood flow in superior vascular loops if any of the descending vasculature is collapsible. If central arterial blood pressure is insufficient to support a blood column between the heart and the head, blood flow ceases because of vascular collapse. Furthermore, the siphon principle does not assist the heart even when a continuous stream of blood is flowing in a superior loop. The potential energy gained by blood as it is pumped to the head is lost to friction in partially collapsed descending vessels and thus is not regained. Application of the Poiseuille equation to flow in collapsible vessels is limited; resistance depends on flow rate in partially collapsed vessels with no transmural pressure difference, but flow rate is independent of resistance. Thus the pressure developed by the heart to establish a given flow rate is independent of the resistance occurring in the partially collapsed vessels. The pressure depends only on the height of the blood column and the resistance in the noncollapsed parts of the system. Simple laboratory models, involving water flow in collapsible tubing, dispel the idea that the siphon principle facilitates blood flow and suggest that previously published results may have been affected by experimental artifact.

scholarly journals Excitatory GABA Responses in Embryonic and Neonatal Cortical Slices Demonstrated by Gramicidin Perforated-Patch Recordings and Calcium Imaging

1996 ◽  
Vol 16 (20) ◽  
pp. 6414-6423 ◽  
Author(s):  
David F. Owens ◽  
Leslie H. Boyce ◽  
Marion B. E. Davis ◽  
Arnold R. Kriegstein
Keyword(s):  
Calcium Imaging ◽  
Perforated Patch ◽  
Excitatory Gaba ◽  
Cortical Slices

Long-Term Imaging Reveals a Circadian Rhythm of Intracellular Chloride in Neurons of the Suprachiasmatic Nucleus

2022 ◽  
pp. 074873042110597
Author(s):  
Nathan J. Klett ◽  
Olga Cravetchi ◽  
Charles N. Allen
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Chloride Concentration ◽  
Intracellular Chloride ◽  
Voltage Gated Calcium Channels ◽  
Excitatory Gaba ◽  
Ratiometric Probe ◽  
Gaba Transmission ◽  
Circadian Physiology ◽  
Intracellular Chloride Concentration

Both inhibitory and excitatory GABA transmission exist in the mature suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. Whether GABA is inhibitory or excitatory depends on the intracellular chloride concentration ([Cl−]i). Here, using the genetically encoded ratiometric probe Cl-Sensor, we investigated [Cl−]i in AVP and VIP-expressing SCN neurons for several days in culture. The chloride ratio (RCl) demonstrated circadian rhythmicity in AVP + neurons and VIP + neurons, but was not detected in GFAP + astrocytes. RCl peaked between ZT 7 and ZT 8 in both AVP + and VIP + neurons. RCl rhythmicity was not dependent on the activity of several transmembrane chloride carriers, action potential generation, or the L-type voltage-gated calcium channels, but was sensitive to GABA antagonists. We conclude that [Cl−]i is under circadian regulation in both AVP + and VIP + neurons.

Intracellular receptors for androgens: Experimental artifact?

Urology ◽  
1983 ◽  
Vol 21 (3) ◽  
pp. 332-333
Author(s):  
Marvin S. Melzer
Keyword(s):  
Experimental Artifact

Excitatory GABA function and its involvement in the NMDA-induced Ca2+ mobilization in the suprachiasmatic nucleus

1998 ◽  
Vol 31 ◽  
pp. S217
Author(s):  
Masayuki Ikeda ◽  
Koji Teshima ◽  
Charles N. Allen ◽  
Tohru Yoshioka
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Excitatory Gaba ◽  
Gaba Function

IS POSTPRANDIAL THERMOPHILY AN EXPERIMENTAL ARTIFACT?

2008 ◽  
Vol 211 (17) ◽  
pp. vii-viii
Author(s):  
J. B. Andersen
Keyword(s):  
Experimental Artifact

scholarly journals GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time

2015 ◽  
Vol 112 (29) ◽  
pp. E3920-E3929 ◽  
Author(s):  
Jihwan Myung ◽  
Sungho Hong ◽  
Daniel DeWoskin ◽  
Erik De Schutter ◽  
Daniel B. Forger ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Synaptic Input ◽  
Chloride Concentration ◽  
Phase Relationship ◽  
Day Length ◽  
Intracellular Chloride ◽  
Circadian Oscillators ◽  
Length Changes ◽  
Excitatory Gaba ◽  
Intracellular Chloride Concentration

The mammalian suprachiasmatic nucleus (SCN) forms not only the master circadian clock but also a seasonal clock. This neural network of ∼10,000 circadian oscillators encodes season-dependent day-length changes through a largely unknown mechanism. We show that region-intrinsic changes in the SCN fine-tune the degree of network synchrony and reorganize the phase relationship among circadian oscillators to represent day length. We measure oscillations of the clock gene Bmal1, at single-cell and regional levels in cultured SCN explanted from animals raised under short or long days. Coupling estimation using the Kuramoto framework reveals that the network has couplings that can be both phase-attractive (synchronizing) and -repulsive (desynchronizing). The phase gap between the dorsal and ventral regions increases and the overall period of the SCN shortens with longer day length. We find that one of the underlying physiological mechanisms is the modulation of the intracellular chloride concentration, which can adjust the strength and polarity of the ionotropic GABAA-mediated synaptic input. We show that increasing day-length changes the pattern of chloride transporter expression, yielding more excitatory GABA synaptic input, and that blocking GABAA signaling or the chloride transporter disrupts the unique phase and period organization induced by the day length. We test the consequences of this tunable GABA coupling in the context of excitation–inhibition balance through detailed realistic modeling. These results indicate that the network encoding of seasonal time is controlled by modulation of intracellular chloride, which determines the phase relationship among and period difference between the dorsal and ventral SCN.

scholarly journals Ketohexokinase: Expression and Localization of the Principal Fructose-metabolizing Enzyme

2009 ◽  
Vol 57 (8) ◽  
pp. 763-774 ◽  
Author(s):  
Christine P. Diggle ◽  
Michael Shires ◽  
Derek Leitch ◽  
David Brooke ◽  
Ian M. Carr ◽  
...  
Keyword(s):  
Western Blotting ◽  
Cellular Localization ◽  
Splice Variants ◽  
Immunohistochemical Localization ◽  
Nuclear Staining ◽  
Experimental Artifact ◽  
Alternatively Spliced ◽  
Metabolizing Enzyme ◽  
Knockout Animals

Ketohexokinase (KHK, also known as fructokinase) initiates the pathway through which most dietary fructose is metabolized. Very little is known about the cellular localization of this enzyme. Alternatively spliced KHK-C and KHK-A mRNAs are known, but the existence of the KHK-A protein isoform has not been demonstrated in vivo. Using antibodies to KHK for immunohistochemistry and Western blotting of rodent tissues, including those from mouse knockouts, coupled with RT-PCR assays, we determined the distribution of the splice variants. The highly expressed KHK-C isoform localized to hepatocytes in the liver and to the straight segment of the proximal renal tubule. In both tissues, cytoplasmic and nuclear staining was observed. The KHK-A mRNA isoform was observed exclusively in a range of other tissues, and by Western blotting, the presence of endogenous immunoreactive KHK-A protein was shown for the first time, proving that the KHK-A mRNA is translated into KHK-A protein in vivo, and supporting the suggestion that this evolutionarily conserved isoform is physiologically functional. However, the low levels of KHK-A expression prevented its immunohistochemical localization within these tissues. Our results highlight that the use of in vivo biological controls (tissues from knockout animals) is required to distinguish genuine KHK immunoreactivity from experimental artifact.

Role of the GABAA receptors in the long-term cognitive impairments caused by neonatal sevoflurane exposure

2019 ◽  
Vol 30 (8) ◽  
pp. 869-879 ◽  
Author(s):  
Tao Li ◽  
Zeyi Huang ◽  
Xianwen Wang ◽  
Ju Zou ◽  
Sijie Tan
Keyword(s):  
Structural Changes ◽  
Cognitive Impairments ◽  
Elevated Serum ◽  
Developmental Abnormalities ◽  
Inhalational Anesthetic ◽  
Excitatory Gaba ◽  
Hpa Axis Activity ◽  
The Brain

Abstract Sevoflurane is a widely used inhalational anesthetic in pediatric surgeries, which is considered reasonably safe and reversible upon withdrawal. However, recent preclinical studies suggested that peri-neonatal sevoflurane exposure may cause developmental abnormalities in the brain. The present review aimed to present and discuss the accumulating experimental data regarding the undesirable effects of sevoflurane on brain development as revealed by the laboratory studies. First, we summarized the long-lasting side effects of neonatal sevoflurane exposure on cognitive functions. Subsequently, we presented the structural changes, namely, neuroapoptosis, neurogenesis and synaptogenesis, following sevoflurane exposure in the immature brain. Finally, we also discussed the potential mechanisms underlying subsequent cognitive impairments later in life, which are induced by neonatal sevoflurane exposure and pointed out potential strategies for mitigating sevoflurane-induced long-term cognitive impairments. The type A gamma-amino butyric acid (GABAA) receptor, the main targets of sevoflurane, is excitatory rather than inhibitory in the immature neurons. The excitatory effects of the GABAA receptors have been linked to increased neuroapoptosis, elevated serum corticosterone levels and epigenetic modifications following neonatal sevoflurane exposure in rodents, which might contribute to sevoflurane-induced long-term cognitive abnormalities. We proposed that the excitatory GABAA receptor-mediated HPA axis activity might be a novel mechanism underlying sevoflurane-induced long-term cognitive impairments. More studies are needed to investigate the effectiveness and mechanisms by targeting the excitatory GABAA receptor as a prevention strategy to alleviate cognitive deficits induced by neonatal sevoflurane exposure in future.

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