scholarly journals Gq DREADD activation of CaMKIIa MnPO neurons stimulates nitric oxide activity

2020 ◽  
Vol 124 (2) ◽  
pp. 591-609
Author(s):  
Alexandria B. Marciante ◽  
George E. Farmer ◽  
J. Thomas Cunningham
Keyword(s):  
Nitric Oxide ◽  
Action Potential ◽  
Designer Drugs ◽  
Preoptic Nucleus ◽  
Adeno Associated Virus ◽  
Nitric Oxide Release ◽  
Median Preoptic Nucleus ◽  
Action Potential Frequency ◽  
Potential Frequency

Rats were injected in the median preoptic nucleus (MnPO) with either an adeno-associated virus (AAV) and excitatory (Gq) designer receptor exclusively activated by designer drugs (DREADD) construct or a control AAV. In the Gq DREADD-injected rats only, clozapine- N-oxide (CNO) increased Fos staining in the MnPO and its targets and increased neuron action potential frequency. In electrophysiology experiments with slices with DREADD cells, unlabeled cells were activated and this was likely due to nitric oxide release by the DREADD cells.

Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus

2007 ◽  
Vol 292 (4) ◽  
pp. R1418-R1428 ◽  
Author(s):  
Debra D. Canabal ◽  
Zhentao Song ◽  
Joseph G. Potian ◽  
Annie Beuve ◽  
Joseph J. McArdle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Action Potential ◽  
Insulin Signaling ◽  
Ventromedial Hypothalamus ◽  
Glucose Sensing ◽  
No Production ◽  
Obesity And Diabetes ◽  
Action Potential Frequency ◽  
Extracellular Glucose ◽  
Potential Frequency

Glucose-sensing neurons in the ventromedial hypothalamus (VMH) are involved in the regulation of glucose homeostasis. Glucose-sensing neurons alter their action potential frequency in response to physiological changes in extracellular glucose, insulin, and leptin. Glucose-excited neurons decrease, whereas glucose-inhibited (GI) neurons increase, their action potential frequency when extracellular glucose is reduced. Central nitric oxide (NO) synthesis is regulated by changes in local fuel availability, as well as insulin and leptin. NO is involved in the regulation of food intake and is altered in obesity and diabetes. Thus this study tests the hypothesis that NO synthesis is a site of convergence for glucose, leptin, and insulin signaling in VMH glucose-sensing neurons. With the use of the NO-sensitive dye 4-amino-5-methylamino-2′,7′-difluorofluorescein in conjunction with the membrane potential-sensitive dye fluorometric imaging plate reader, we found that glucose and leptin suppress, whereas insulin stimulates neuronal nitric oxide synthase (nNOS)-dependent NO production in cultured VMH GI neurons. The effects of glucose and leptin were mediated by suppression of AMP-activated protein kinase (AMPK). The AMPK activator 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) increased both NO production and neuronal activity in GI neurons. In contrast, the effects of insulin on NO production were blocked by the phosphoinositide 3-kinase inhibitors wortmannin and LY-294002. Furthermore, decreased glucose, insulin, and AICAR increase the phosphorylation of VMH nNOS, whereas leptin decreases it. Finally, VMH neurons express soluble guanylyl cyclase, a downstream mediator of NO signaling. Thus NO may mediate, in part, glucose, leptin, and insulin signaling in VMH glucose-sensing neurons.

Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus

2004 ◽  
Vol 101 (3) ◽  
pp. 511-517 ◽  
Author(s):  
Kendall H. Lee ◽  
Su-Youne Chang ◽  
David W. Roberts ◽  
Uhnoh Kim
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Neurotransmitter Release ◽  
High Frequency Stimulation ◽  
Content Type ◽  
Action Potential Frequency ◽  
Frequency Stimulation ◽  
Potential Frequency ◽  
Fine Print ◽  
Stimulation Of

Object. High-frequency stimulation (HFS) delivered through implanted electrodes in the subthalamic nucleus (STN) has become an established treatment for Parkinson disease (PD). The precise mechanism of action of deep brain stimulation (DBS) in the STN is unknown, however. In the present study, the authors tested the hypothesis that HFS within the STN changes neuronal action potential firing rates during the stimulation period by modifying neurotransmitter release. Methods. Intracellular electrophysiological recordings were obtained using sharp electrodes in rat STN neurons in an in vitro slice preparation. A concentric bipolar stimulating electrode was placed in the STN slice, and electrical stimulation (pulse width 50–100 µsec, duration 100–2000 µsec, amplitude 10–500 µA, and frequency 10–200 Hz) was delivered while simultaneously obtaining intracellular recordings from an STN neuron. High-frequency stimulation of the STN either generated excitatory postsynaptic potentials (EPSPs) and increased the action potential frequency or it generated inhibitory postsynaptic potentials and decreased the action potential frequency of neurons within the STN. These effects were blocked after antagonists to glutamate and γ-aminobutyric acid were applied to the tissue slice, indicating that HFS resulted in the release of neurotransmitters. Intracellular recordings from substantia nigra pars compacta (SNc) dopaminergic neurons during HFS of the STN revealed increased generation of EPSPs and increased frequency of action potentials in SNc neurons. Conclusions. During HFS of STN neurons the mechanism of DBS may involve the release of neurotransmitters rather than the primary electrogenic inhibition of neurons.

Contribution of individual ionic currents to activity of a model stomatogastric ganglion neuron

1992 ◽  
Vol 67 (2) ◽  
pp. 341-349 ◽  
Author(s):  
J. Golowasch ◽  
F. Buchholtz ◽  
I. R. Epstein ◽  
E. Marder
Keyword(s):  
Action Potential ◽  
Model Neuron ◽  
Outward Current ◽  
Rhythmic Activity ◽  
Stomatogastric Ganglion ◽  
Delayed Rectifier ◽  
Maximal Conductance ◽  
Action Potential Frequency ◽  
Potential Frequency

1. The behavior of the mathematical model for the lateral pyloric (LP) neuron of the crustacean stomatogastric ganglion (STG) developed in the previous paper was further studied. 2. The action of proctolin, a neuromodulatory peptide that acts directly on the LP neuron, was modeled. The effect of the proctolin-activated current (iproc) on the model neuron mimics the effects of proctolin on the isolated biological LP neuron. The depolarization and increased frequency of firing seen when iproc is activated are associated with changes in the relative contributions of the delayed rectifier (id) and the Ca(2+)-activated outward current (io(Ca] to the repolarization phase of the action potential. 3. The effects of turning off the A-current (iA) in the model were compared with those obtained by pharmacologically blocking iA in the biological neuron. iA appears to regulate action-potential frequency as well as postinhibitory rebound activity. 4. The role of iA on the rhythmic activity of the cell was studied by modifying several of its parameters while periodically activating a simulated synaptically activated conductance, isyn. 5. The effects of manipulations of the maximal conductances (g) for id and io(Ca) were studied. id strongly influences action-potential frequency, whereas io(Ca) strongly influences action-potential duration. 6. Modifications of the maximal conductance of the inward Ca2+ current (iCa) were compared with the effects of blocking iCa in the real cell. 7. The role of the hyperpolarization-activated inward current (ih) during ongoing rhythmic activity was assessed by periodically activating isyn while modifying ih.

scholarly journals Correlation between electrical activity and ACTH/beta-endorphin secretion in mouse pituitary tumor cells.

1982 ◽  
Vol 95 (2) ◽  
pp. 559-566 ◽  
Author(s):  
A Surprenant
Keyword(s):  
Action Potential ◽  
Tumor Cells ◽  
Action Potentials ◽  
Hormone Secretion ◽  
Secretory Activity ◽  
Beta Endorphin ◽  
Action Potential Frequency ◽  
Potential Activity ◽  
Mouse Pituitary ◽  
Potential Frequency

The electrical and secretory activities of mouse pituitary tumor cells (AtT-20/D-16v), which contain and release the ACTH/beta-endorphin family of peptides, were studied by means of intracellular recordings and radioimmunoassays. Injection of depolarizing current pulses evoked action potentials in all cells and the majority (82%) displayed spontaneous action potential activity. Action potentials were found to be calcium-dependent. Barium increased membrane resistance, action potential amplitude and duration, and release of ACTH and beta-endorphin immunoactivity. Isoproterenol increased both action potential frequency and hormone secretion. Raising the external calcium concentration increased the frequency and amplitude of the action potentials and stimulated secretion of ACTH and beta-endorphin immunoactivity. Thus, stimulation of secretory activity in AtT-20 cells was closely correlated with increased electrical activity. However, a complete blockade of action potential activity had no effect on basal hormone secretion in these cells. These results suggest that the mechanisms underlying stimulated hormone secretion are different from those responsible for basal secretory activity. It is proposed that the increased influx of calcium due to the increased action potential frequency initiates the stimulated release of hormone from these cells.

Chronic hypercapnia resets CO2 sensitivity of avian intrapulmonary chemoreceptors

1999 ◽  
Vol 276 (2) ◽  
pp. R317-R322 ◽  
Author(s):  
D. E. Bebout ◽  
S. C. Hempleman
Keyword(s):  
Action Potential ◽  
Discharge Rate ◽  
Control Of Breathing ◽  
Neural Responses ◽  
Acid Base ◽  
Co2 Sensitivity ◽  
Action Potential Frequency ◽  
Intrapulmonary Chemoreceptors ◽  
Text Retention ◽  
Potential Frequency

Avian intrapulmonary chemoreceptors (IPC) are vagal sensory neurons that participate in the control of breathing. IPC action potential frequency is inversely proportional to [Formula: see text], but it is unclear whether low [Formula: see text] or high pH is the immediate stimulus for signal transduction in IPC. To address this question, comparisons were made between single cell neural responses of 34 IPC recorded in 6 anesthetized ducks ( Anas platyrhynchos) acclimatized 12 days to 7.5% inspired CO2 and 22 IPC recorded in 9 normal anesthetized ducks. We hypothesized that if respiratory-linked pH changes determine IPC activity, action potential frequency as a function of inspiratory[Formula: see text]([Formula: see text]) should be greater after acclimatization due to metabolic acid-base compensation and higher pH. Conversely, if[Formula: see text] alone determines IPC discharge, action potential frequency vs.[Formula: see text] should be unchanged by acclimatization. Results indicate that after acclimatization ventilation was depressed at 28 and 42 Torr[Formula: see text]( P < 0.05) and mean plasma pH at 40 Torr [Formula: see text] increased from 7.38 ± 0.03 to 7.56 ± 0.02 ( P < 0.05), indicating significant metabolic acid-base compensation and[Formula: see text] retention. Mean IPC discharge rate was elevated by CO2acclimatization at all [Formula: see text] studied. In acclimatized vs. normal animals, regression analysis of IPC discharge as a function of[Formula: see text] showed increased mean intercepts of 81.1 ± 4.0 vs. 48.4 ± 3.6 impulses/s ( P < 0.05) and increased mean slopes of −19.0 ± 1.0 vs. −12.0 ± 1.1 impulses ⋅ s−1 ⋅ [Formula: see text] −1( P < 0.05). Results indicate that IPC response to CO2 is mediated by H+ from CO2 hydration and not by CO2 directly.

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