Selective stimulation of type-1 or type-2 responses precedes and matches the autoimmune diseases triggered by the chemicals streptozotocin and HgCl2

1997 ◽  
Vol 56 (1-3) ◽  
pp. 308
Author(s):  
R Albers
Keyword(s):  
Autoimmune Diseases ◽  
Selective Stimulation ◽  
Stimulation Of

scholarly journals Differential expression and regulation of ryanodine receptor and myo-inositol 1,4,5-trisphosphate receptor Ca2+ release channels in mammalian tissues and cell lines

1997 ◽  
Vol 327 (1) ◽  
pp. 251-258 ◽  
Author(s):  
John J. MACKRILL ◽  
R. A. John CHALLISS ◽  
D. A. O'CONNELL ◽  
F. Anthony LAI ◽  
Stefan R. NAHORSKI
Keyword(s):  
Cell Lines ◽  
Mammalian Cell ◽  
Release Channel ◽  
Chronic Stimulation ◽  
Channel Proteins ◽  
Mammalian Cell Lines ◽  
Rabbit Tissues ◽  
Stimulation Of

Ryanodine receptors (RyRs) and Ins(1,4,5)P3 receptors (Ins(1,4,5)P3Rs) represent two multigene families of channel proteins that mediate the release of Ca2+ ions from intracellular stores. In the present study, the expression patterns of these channel proteins in mammalian cell lines and tissues were investigated by using isoform-specific antibodies. All cell lines examined expressed two or more Ins(1,4,5)P3R isoforms, with the type 1 Ins(1,4,5)P3R being ubiquitous. RyR isoforms were detected in only six out of eight cell lines studied. Similarly, of the nine rabbit tissues examined, RyR protein expression was detected only in brain, heart, skeletal muscle and uterus. Specific [3H]ryanodine binding was found in a number of rabbit tissues, although it was not detected in mammalian cell lines. Subcellular fractionation of SH-SY5Y human neuroblastomas revealed that the type 2 RyR and type 1 Ins(1,4,5)P3R co-localize among the fractions of a sucrose-cushion separation of crude microsomal membrane fractions. Manipulation of SH-SY5Y cells by chronic stimulation of muscarinic acetylcholine receptor (mAChR) results in a decrease in their type 1 Ins(1,4,5)P3R levels but not in the abundance of the type 2 RyR. Differentiation of these neuroblastomas by using retinoic acid did not detectably alter their expression of Ca2+-release channel proteins. Finally, differentiation of BC3H1 cells affects the expression of their Ca2+-release channel proteins in an isoform-specific manner. In summary, this study demonstrates that mammalian cell lines display distinct patterns of Ca2+-release channel protein expression. The abundance of these proteins is differentially regulated during phenotypic modifications of a cell, such as differentiation or chronic stimulation of mAChR.

Excitatory Synaptic Currents in Lumbosacral Parasympathetic Preganglionic Neurons Evoked by Stimulation of the Dorsal Commissure

2003 ◽  
Vol 89 (1) ◽  
pp. 382-389 ◽  
Author(s):  
Akira Miura ◽  
Masahito Kawatani ◽  
William C. De Groat
Keyword(s):  
Time Constant ◽  
Decay Time ◽  
Fast Component ◽  
Time To Peak ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship ◽  
Stimulation Of

Excitatory pathways from the dorsal commissure (DCM) to L6–S1 parasympathetic preganglionic neurons (PGN) were examined using whole-cell patch-clamp recording techniques in spinal cord slices from neonatal rats. PGN were identified by retrograde axonal transport of a fluorescent dye injected into the intraperitoneal space. Excitatory postsynaptic currents (EPSCs) were evoked in PGN by stimulation of DCM in the presence of bicuculline methiodide (10 μM) and strychnine (1 μM) to block inhibitory pathways. Electrical stimulation of DCM evoked two types of inward currents. In the majority of PGN ( n = 66), currents (mean amplitude, 47.9 ± 4.7 pA) occurred at a short and relatively constant latency (3.8 ± 0.1 ms) and presumably represent monosynaptic EPSCs (Type 1). However, in other neurons ( n = 20), a different type of EPSC (Type 2) was noted, consisting of a fast monosynaptic component followed by a prolonged inward current with superimposed fast transients presumably representing excitatory inputs mediated by polysynaptic pathways. Type 1 EPSCs were pharmacologically dissected into two components. A fast component was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5μM) and a slowly decaying component was blocked by 2-amino-5-phosphonovalerate (APV, 50 μM). The fast component of Type 1 EPSCs had a linear current-voltage relationship and reversed at a membrane potential of −7.6 ± 1.3 mV ( n = 5). The fast component of Type 2 EPSCs was also blocked by 5 μM CNQX and the remaining slower component was blocked by 50 μM APV. When the DCM was stimulated in the presence of 50 μM APV, the time to peak and decay time constant in Type 1 EPSCs were 1.9 ± 0.2 and 4.1 ± 0.8 ms, respectively. Examination of the NMDA receptor-mediated component of the EPSCs in the presence of 5 μM CNQX revealed a current-voltage relationship that had a region of negative slope conductance (from −20 to −80 mV), which was abolished in Mg2+-free external solution. The time to peak and decay time constant of this component were 14.2 ± 2.0 and 91.0 ± 12.4 ms, respectively. Type 1 EPSCs in some PGN responded in an all-or-none manner and presumably represented unitary synaptic responses; whereas Type 2 EPSCs always exhibited a graded stimulus intensity–response relationship. Paired-pulse facilitation (50-ms interstimulus intervals; 141 ± 5.6% increase, n = 8) of EPSCs was observed. These results indicate that PGN receive monosynaptic and polysynaptic glutamatergic excitatory inputs from neurons and/or axonal pathways in the DCM.

Synaptic inputs to morphologically identified myenteric neurons in guinea pig rectum from pelvic nerves

1997 ◽  
Vol 273 (1) ◽  
pp. G49-G55 ◽  
Author(s):  
K. Tamura
Keyword(s):  
Morphological Characteristics ◽  
Pelvic Nerve ◽  
Low Frequencies ◽  
Myenteric Neurons ◽  
Synaptic Inputs ◽  
Pelvic Nerves ◽  
Single Spike ◽  
Stimulation Of

Neurobiotin-filled microelectrodes were used to investigate electrical and synaptic behavior and morphological characteristics of rectal myenteric neurons that received synaptic inputs from the pelvic nerves. Stimulation of the pelvic nerve at low frequencies (< 3.3 Hz) evoked nicotinic fast excitatory postsynaptic potentials (fast EPSPs) in 45.3% of rectal neurons. Pelvic fast EPSPs were found in S/type 1, AH/type 2, type 3, or single-spike neurons that had a single long process preferentially projecting in the orad direction. Stimulation of the pelvic nerve at higher frequencies (5–20 Hz) elicited slow membrane excitation in 13.9% of the neurons. They were either AH/type 2 neurons with Dogiel II morphology or S/type 1 neurons with a single long process. Hexamethonium (100 microM) blocked pelvic fast EPSPs more quickly than those evoked by fiber tract stimulation but did not affect slow excitatory response. The results suggested the presence of more than one nicotinic-cholinergic synapse in the pelvic nerve pathway and the possible release of a noncholinergic excitatory substance from the afferent nerve terminals. It is possible that a subpopulation of rectal neurons, which receive a fast EPSP and have a single long process that projects in the orad direction, might be interneurons that mediate the defecation reflex.

Glutamate-mediated slow synaptic currents in neonatal rat deep dorsal horn neurons in vitro

1996 ◽  
Vol 76 (3) ◽  
pp. 1465-1476 ◽  
Author(s):  
B. A. Miller ◽  
C. J. Woolf
Keyword(s):  
Dorsal Horn ◽  
Slow Component ◽  
Small Diameter ◽  
Primary Afferents ◽  
Neonatal Rat ◽  
Dorsal Horn Neurons ◽  
Stimulation Of

1. The role of glutamate in slow excitatory synaptic transmission between small-diameter primary afferents and deep dorsal horn neurons was examined in neonatal rat spinal cord in vitro with the use of the whole cell voltage-clamp technique. 2. Single-shock electrical stimulation of large-diameter A beta-fibers evoked a short-latency (< 10 ms) fast (< 500 ms) excitatory postsynaptic current (EPSC). Stimulation of small-diameter A delta- and C fibers resulted, in addition, in a slowly rising and decaying EPSC (lasting up to 14 s) following the fast EPSC. The slow EPSC was never observed with stimulation of A beta-fibers. 3. Two patterns of EPSCs were observed, "type 1" and "type 2," which differed in their time course (lasting up to 1 and 14 s, respectively). The type 1 response was biphasic, with a fast monosynaptic component followed by an invariant, presumably monosynaptic, late slow component. The type 2 response was multiphasic, with a fast monosynaptic component followed by a slow component composed of fast polysynaptic currents superimposed on a slow current. 4. The fast monosynaptic component had a linear conductance, whereas the late slower component of the A beta-fiber-evoked response had a negative slope conductance at holding potentials more negative than -23 mV. Both currents reversed at a membrane potential of -1.2 +/- 2.8 (SE) mV. 5. With the use of selective non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor antagonists [6-cyano-7-nitroquinox-aline-2,3-dione (CNQX) or 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F) quinoxaline and D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), respectively] we showed that both the early fast (A beta-fiber evoked) and the late slow (A delta- and C fiber evoked) components were mediated by non-NMDA and NMDA receptors. CNQX suppressed both the early fast and late slow components of the compound EPSC, whereas D-AP5 suppressed the polysynaptic currents of the early fast component and the late slow component without significantly affecting the early fast monosynaptic component. 6. Slow EPSCs summated on low-frequency (1 or 10 Hz), repetitive stimulation and produced long-duration "tail" currents on cessation of the stimulus. The amount of temporal summation was proportional to the duration of the slow EPSC and the frequency of stimulation. 7. Our results suggest that slow ionotropic-glutamate-receptor-mediated EPSCs produced by the stimulation of small-diameter primary afferents play an important role in activity-dependent synaptic plasticity in the dorsal horn.

Comorbidity between central disorders of hypersomnolence and immune-based disorders

Neurology ◽  
2016 ◽  
Vol 88 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Lucie Barateau ◽  
Régis Lopez ◽  
Isabelle Arnulf ◽  
Michel Lecendreux ◽  
Patricia Franco ◽  
...  
Keyword(s):  
Family History ◽  
Autoimmune Diseases ◽  
Positive Family History ◽  
Autoinflammatory Disorders ◽  
Increased Risk ◽  
Idiopathic Hypersomnia ◽  
History Of ◽  
Adults And Children

Objective:To assess and compare the frequencies of personal and family history of autoimmune diseases (AID), autoinflammatory disorders (ID), and allergies in a population of patients, adults and children, with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), 3 central hypersomnia disorders, and healthy controls.Methods:Personal and family history of AID, ID, and allergies were assessed by questionnaire and medical interview in a large cohort of 450 consecutive adult patients (206 NT1, 106 NT2, 138 IH) and 95 pediatric patients (80 NT1) diagnosed according to the third International Classification of Sleep Disorders criteria in national reference centers for narcolepsy in France and 751 controls (700 adults, 51 children) from the general population.Results:Ten adults with NT1 (4.9%) had a comorbid AID vs 3.4% of adult controls, without between-group differences in adjusted models. AID frequency did not differ between children with NT1 and controls. Conversely, compared with controls, AID frequency was higher in adults with NT2 (p = 0.002), whereas ID (p = 0.0002) and allergy (p = 0.003) frequencies were higher in adults with IH. A positive family history of AID was found in the NT1 group and of ID in the IH group.Conclusions:NT1 is not associated with increased risk of comorbid immune disorders, in favor of a potentially unique pathophysiology. Conversely, compared with controls, the frequency of autoimmune diseases was higher in adults with NT2, whereas allergies and autoinflammatory disorders were more common in adults with IH, suggesting an immune dysregulation mechanism in these conditions.

Hyperinsulinaemia is Associated with Stimulation of Cholesterol Synthesis in Both Type 1 and Type 2 Diabetes

1993 ◽  
Vol 10 (5) ◽  
pp. 412-419 ◽  
Author(s):  
J.C. Stinson ◽  
D. Owens ◽  
P. Collins ◽  
A. Johnson ◽  
G.H. Tomkin
Keyword(s):  
Type 2 Diabetes ◽  
Cholesterol Synthesis ◽  
Stimulation Of
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