Glycine Receptors Mediate Excitation of Subplate Neurons in Neonatal Rat Cerebral Cortex

2008 ◽  
Vol 100 (2) ◽  
pp. 698-707 ◽  
Author(s):  
W. Kilb ◽  
I. L. Hanganu ◽  
A. Okabe ◽  
B. A. Sava ◽  
C. Shimizu-Okabe ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Network Activity ◽  
Glycine Receptors ◽  
Excitatory Effect ◽  
Early Postnatal Development ◽  
Perforated Patch ◽  
Subplate Neurons ◽  
Inward Currents

The development of the cerebral cortex depends on genetic factors and early electrical activity patterns that form immature neuronal networks. Subplate neurons (SPn) are involved in the construction of thalamocortical innervation, generation of oscillatory network activity, and in the proper formation of the cortical columnar architecture. Because glycine receptors play an important role during early corticogenesis, we analyzed the functional consequences of glycine receptor activation in visually identified SPn in neocortical slices from postnatal day 0 (P0) to P4 rats using whole cell and perforated patch-clamp recordings. In all SPn the glycinergic agonists glycine, β-alanine, and taurine induced dose-dependent inward currents with the affinity for glycine being higher than that for β-alanine and taurine. Glycine-induced responses were blocked by the glycinergic antagonist strychnine, but were unaffected by either the GABAergic antagonist gabazine, the N-methyl-d-aspartate–receptor antagonist d-2-amino-5-phosphonopentanoic acid, or picrotoxin and cyanotriphenylborate, antagonists of α-homomeric and α1-subunit–containing glycine receptors, respectively. Under perforated-patch conditions, glycine induced membrane depolarizations that were sufficient to trigger action potentials (APs) in most cells. Furthermore, glycine and taurine decreased the injection currents as well as the synaptic stimulation strength required to elicit APs, indicating that glycine receptors have a consistent excitatory effect on SPn. Inhibition of taurine transport and application of hypoosmolar solutions induced strychnine-sensitive inward currents, suggesting that taurine can act as a possible endogenous agonist on SPn. In summary, these results demonstrate that SPn express glycine receptors that mediate robust excitatory membrane responses during early postnatal development.

Na+-K+-2Cl− Cotransporter in Immature Cortical Neurons: A Role in Intracellular Cl−Regulation

1999 ◽  
Vol 81 (4) ◽  
pp. 1939-1948 ◽  
Author(s):  
Dandan Sun ◽  
Sangita G. Murali
Keyword(s):  
Cerebral Cortex ◽  
Cortical Neurons ◽  
Immunocytochemical Staining ◽  
Excitatory Effect ◽  
Rat Fetus ◽  
Early Postnatal Development ◽  
Steady Level ◽  
Early Developmental ◽  
Dependent Mechanism

Na+-K+-2Cl− cotransporter in immature cortical neurons: a role in intracellular Cl−regulation. Na+-K+-2Cl−cotransporter has been suggested to contribute to active intracellular Cl− accumulation in neurons at both early developmental and adult stages. In this report, we extensively characterized the Na+-K+-2Cl− cotransporter in primary culture of cortical neurons that were dissected from cerebral cortex of rat fetus at embryonic day 17. The Na+-K+-2Cl− cotransporter was expressed abundantly in soma and dendritic processes of cortical neurons evaluated by immunocytochemical staining. Western blot analysis revealed that an ∼145-kDa cotransporter protein was present in cerebral cortex at the early postnatal (P0–P9) and adult stages. There was a time-dependent upregulation of the cotransporter activity in cortical neurons during the early postnatal development. A substantial level of bumetanide-sensitive K+ influx was detected in neurons cultured for 4–8 days in vitro (DIV 4–8). The cotransporter activity was increased significantly at DIV 12 and maintained at a steady level throughout DIV 12–14. Bumetanide-sensitive K+influx was abolished completely in the absence of either extracellular Na+ or Cl−. Opening of γ-aminobutyric acid (GABA)-activated Cl− channel or depletion of intracellular Cl− significantly stimulated the cotransporter activity. Moreover, the cotransporter activity was elevated significantly by activation of N-methyl-d-aspartate ionotropic glutamate receptor via a Ca2+-dependent mechanism. These results imply that the inwardly directed Na+-K+-2Cl− cotransporter is important in active accumulation of intracellular Cl− and may be responsible for GABA-mediated excitatory effect in immature cortical neurons.

Muscarinic and Nicotinic ACh Receptor Activation Differentially Mobilize Ca2+ in Rat Intracardiac Ganglion Neurons

2003 ◽  
Vol 90 (3) ◽  
pp. 1956-1964 ◽  
Author(s):  
Friederike Beker ◽  
Martin Weber ◽  
Rainer H. A. Fink ◽  
David J. Adams
Keyword(s):  
Receptor Activation ◽  
Neonatal Rat ◽  
Induced Response ◽  
Induced Responses ◽  
Outward Currents ◽  
Cell Recording ◽  
Intracellular Ca ◽  
Inward Currents ◽  
Ganglion Neurons ◽  
Intracardiac Neurons

The origin of intracellular Ca2+ concentration ([Ca2+]i) transients stimulated by nicotinic (nAChR) and muscarinic (mAChR) receptor activation was investigated in fura-2-loaded neonatal rat intracardiac neurons. ACh evoked [Ca2+]i increases that were reduced to ∼60% of control in the presence of either atropine (1 μM) or mecamylamine (3 μM) and to <20% in the presence of both antagonists. Removal of external Ca2+ reduced ACh-induced responses to 58% of control, which was unchanged in the presence of mecamylamine but reduced to 5% of control by atropine. The nAChR-induced [Ca2+]i response was reduced to 50% by 10 μM ryanodine, whereas the mAChR-induced response was unaffected by ryanodine, suggesting that Ca2+ release from ryanodine-sensitive Ca2+ stores may only contribute to the nAChR-induced [Ca2+]i responses. Perforated-patch whole cell recording at –60 mV shows that the rise in [Ca2+]i is concomitant with slow outward currents on mAChR activation and with rapid inward currents after nAChR activation. In conclusion, different signaling pathways mediate the rise in [Ca2+]i and membrane currents evoked by ACh binding to nicotinic and muscarinic receptors in rat intracardiac neurons.

scholarly journals Mechanisms of L-Triiodothyronine-Induced Inhibition of Synaptosomal Na+-K+-ATPase Activity in Young Adult Rat Brain Cerebral Cortex

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Pradip K. Sarkar ◽  
Avijit Biswas ◽  
Arun K. Ray ◽  
Joseph V. Martin
Keyword(s):  
Cerebral Cortex ◽  
Atpase Activity ◽  
Adrenergic Receptor ◽  
Receptor Activation ◽  
Mammalian Brain ◽  
Neuronal Membrane ◽  
Dependent Manner ◽  
Adrenergic Agonist ◽  
Adult Rat ◽  
Dose Dependent

The role of thyroid hormones (TH) in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na+-K+-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na+-K+-ATPase activity (but not Mg2+-ATPase activity) in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3and theβ-adrenergic agonist isoproterenol inhibited Na+-K+-ATPase activity in cerebrocortical synaptosomes in similar ways, theβ-adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na+-K+-ATPase activity in a dose-dependent manner, suggesting that the effect of T3on synaptosomal Na+-K+-ATPase activity was independent ofβ-adrenergic receptor activation. The effect of T3on synaptosomal Na+-K+-ATPase activity was inhibited by theα2-adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activateGi-proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition.

scholarly journals Optogenetic currents in myofibroblasts acutely alter electrophysiology and conduction of co-cultured cardiomyocytes

2020 ◽  
Author(s):  
Geran Kostecki ◽  
Yu Shi ◽  
Christopher Chen ◽  
Daniel H. Reich ◽  
Emilia Entcheva ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Cardiac Injury ◽  
Neonatal Rat ◽  
Culture Studies ◽  
Electrophysiological Properties ◽  
Inward Currents ◽  
Life Threatening ◽  
Cultured Cardiomyocytes ◽  
Cardiac Myofibroblasts

AbstractInteractions between cardiac myofibroblasts and myocytes may slow conduction after cardiac injury, increasing the chance of life-threatening arrhythmia. While co-culture studies have shown that myofibroblasts can affect cardiomyocyte electrophysiology in vitro, the mechanism(s) remain debatable. In this study, primary neonatal rat cardiac myofibroblasts were transduced with the light-activated ion channel Channelrhodopsin-2, which allowed acute and selective modulation of myofibroblast currents in co-cultures with cardiomyocytes. Optical mapping revealed that myofibroblast-specific optogenetically induced inward currents decreased conduction velocity in the co-cultures by 27±6% (baseline = 17.7±5.3 cm/s), and shortened the cardiac action potential duration by 14±7% (baseline = 161±11 ms) when 0.017 mW/mm2 light was applied. When light irradiance was increased to 0.057 mW/mm2, the myofibroblast currents led to spontaneous beating in 6/7 co-cultures. Experiments showed that optogenetic perturbation did not lead to changes in myofibroblast strain and force generation, suggesting purely electrical effects in this model. In silico modeling of optogenetically modified myofibroblast-cardiomyocyte co-cultures largely reproduced these results and enabled a comprehensive study of relevant parameters. These results clearly demonstrate that myofibroblasts are sufficiently electrically connected to cardiomyocytes to effectively alter macroscopic electrophysiological properties in this model of cardiac tissue.

Domoic acid, the alleged "mussel toxin," might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the rat dorsal hippocampus

1989 ◽  
Vol 67 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Guy Debonnel ◽  
Luc Beauchesne ◽  
Claude de Montigny
Keyword(s):  
Amino Acid ◽  
Domoic Acid ◽  
Pyramidal Neurons ◽  
Excitatory Amino Acid ◽  
Dorsal Hippocampus ◽  
Electrophysiological Study ◽  
Receptor Activation ◽  
Kainate Receptor ◽  
Neurotoxic Effect ◽  
Excitatory Effect

Domoic acid, an excitatory amino acid structurally related to kainate, was recently identified as being presumably responsible for the recent severe intoxication presented by more than 100 people having eaten mussels grown in Prince Edward Island (Canada). The amino acid kainate has been shown to be highly neurotoxic to the hippocampus, which is the most sensitive structure in the central nervous system. The present in vivo electrophysiological studies were undertaken to determine if domoic acid exerts its neurotoxic effect via kainate receptor activation. Unitary extracellular recordings were obtained from pyramidal neurons of the CA1 and the CA3 regions of the rat dorsal hippocampus. The excitatory effect of domoic acid applied by microiontophoresis was compared with that of agonists of the three subtypes of glutamatergic receptors: kainate, quisqualate, and N-methyl-D-aspartate. In CA1, the activation induced by domoic acid was about threefold greater than that induced by kainate; identical concentrations and similar currents were used. In CA3, domoic acid was also three times more potent than kainate. However, the most striking finding was that domoic acid, similar to kainate, was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with quisqualate and N-methyl-D-aspartate. As the differential regional response of CA1 and CA3 pyramidal neurons to kainate is attributable to the extremely high density of kainate receptors in the CA3 region, these results provide the first electrophysiological evidence that domoic acid may produce its neurotoxic effects through kainate receptor activation.Key words: domoate, kainate, excitotoxin, hippocampus, N-methyl-D-aspartate.

scholarly journals Thyroid hormone regulated genes in cerebral cortex development

2017 ◽  
Vol 232 (2) ◽  
pp. R83-R97 ◽  
Author(s):  
Juan Bernal
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormones ◽  
Fetal Development ◽  
Cell Types ◽  
Control Of Gene Expression ◽  
Cellular Targets ◽  
Cerebral Cortex Development ◽  
Subplate Neurons ◽  
Genes Encoding

The physiological and developmental effects of thyroid hormones are mainly due to the control of gene expression after interaction of T3 with the nuclear receptors. To understand the role of thyroid hormones on cerebral cortex development, knowledge of the genes regulated by T3 during specific stages of development is required. In our laboratory, we previously identified genes regulated by T3 in primary cerebrocortical cells in culture. By comparing these data with transcriptomics of purified cell types from the developing cortex, the cellular targets of T3 can be identified. In addition, many of the genes regulated transcriptionally by T3 have defined roles in cortex development, from which the role of T3 can be derived. This review analyzes the specific roles of T3-regulated genes in the different stages of cortex development within the physiological frame of the developmental changes of thyroid hormones and receptor concentrations in the human cerebral cortex during fetal development. These data indicate an increase in the sensitivity to T3 during the second trimester of fetal development. The main cellular targets of T3 appear to be the Cajal-Retzius and the subplate neurons. On the other hand, T3 regulates transcriptionally genes encoding extracellular matrix proteins, involved in cell migration and the control of diverse signaling pathways.

Dynorphin A Elicits an Increase in Intracellular Calcium in Cultured Neurons Via a Non-Opioid, Non-NMDA Mechanism

2000 ◽  
Vol 83 (5) ◽  
pp. 2610-2615 ◽  
Author(s):  
Qingbo Tang ◽  
Ronald M. Lynch ◽  
Frank Porreca ◽  
Josephine Lai
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Intracellular Calcium ◽  
Cortical Neurons ◽  
Excitatory Amino Acid ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Dynorphin A ◽  
Excitatory Effect

The opioid peptide dynorphin A is known to elicit a number of pathological effects that may result from neuronal excitotoxicity. An up-regulation of this peptide has also been causally related to the dysesthesia associated with inflammation and nerve injury. These effects of dynorphin A are not mediated through opioid receptor activation but can be effectively blocked by pretreatment with N-methyl-d-aspartate (NMDA) receptor antagonists, thus implicating the excitatory amino acid system as a mediator of the actions of dynorphin A and/or its fragments. A direct interaction between dynorphin A and the NMDA receptors has been well established; however the physiological relevance of this interaction remains equivocal. This study examined whether dynorphin A elicits a neuronal excitatory effect that may underlie its activation of the NMDA receptors. Calcium imaging of individual cultured cortical neurons showed that the nonopioid peptide dynorphin A(2-17) induced a time- and dose-dependent increase in intracellular calcium. This excitatory effect of dynorphin A(2-17) was insensitive to (+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a,d]-cyclohepten-5,10-imine (MK-801) pretreatment in NMDA-responsive cells. Thus dynorphin A stimulates neuronal cells via a nonopioid, non-NMDA mechanism. This excitatory action of dynorphin A could modulate NMDA receptor activity in vivo by enhancing excitatory neurotransmitter release or by potentiating NMDA receptor function in a calcium-dependent manner. Further characterization of this novel site of action of dynorphin A may provide new insight into the underlying mechanisms of dynorphin excitotoxicity and its pathological role in neuropathy.

GAT-1 and Reversible GABA Transport in Bergmann Glia in Slices

2002 ◽  
Vol 88 (3) ◽  
pp. 1407-1419 ◽  
Author(s):  
L. Barakat ◽  
A. Bordey
Keyword(s):  
Gaba Receptors ◽  
Receptor Activation ◽  
Bergmann Glia ◽  
Gaba Uptake ◽  
Induced Voltage ◽  
Nipecotic Acid ◽  
Gaba Transporters ◽  
Whole Cell Patch Clamp ◽  
Inward Currents

Although glial GABA uptake and release have been studied in vitro, GABA transporters (GATs) have not been characterized in glia in slices. Whole cell patch-clamp recordings were obtained from Bergmann glia in rat cerebellar slices to characterize carrier-mediated GABA influx and efflux. GABA induced inward currents at −70 mV that could be pharmacologically separated into GABAA receptor and GAT currents. In the presence of GABAA/B/C receptor blockers, mean GABA-induced currents measured −48 pA at −70 mV, were inwardly rectifying between −70 and +50 mV, were inhibited by external Na+ removal, and were diminished by reduction of external Cl−. Nontransportable blockers of GAT-1 (SKF89976-A and NNC-711) and a transportable blocker of all the GAT subtypes (nipecotic acid) reversibly reduced GABA-induced transport currents by 68 and 100%, respectively. A blocker of BGT-1 (betaine) had no effect. SKF89976-A and NNC-711 also suppressed baseline inward currents that likely result from tonic GAT activation by background GABA. The substrate agonists, nipecotic acid and β-alanine but not betaine, induced voltage- and Na+-dependent currents. With Na+ and GABA inside the patch pipette or intracellular GABA perfusion during the recording, SKF89976-A blocked baseline outward currents that activated at −60 mV and increased with more depolarized potentials. This carrier-mediated GABA efflux induced a local accumulation of extracellular GABA detected by GABAA receptor activation on the recorded cell. Overall, these results indicate that Bergmann glia express GAT-1 that are activated by ambient GABA. In addition, GAT-1 in glia can work in reverse and release sufficient GABA to activate nearby GABA receptors.

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