scholarly journals Contributing mechanisms underlying desensitization of cholecystokinin-induced activation of primary nodose ganglia neurons

2020 ◽  
Vol 318 (4) ◽  
pp. C787-C796 ◽  
Author(s):  
Cody W. Kowalski ◽  
Jonathan E. M. Lindberg ◽  
Daniel K. Fowler ◽  
Steven M. Simasko ◽  
James H. Peters
Keyword(s):  
Ion Channel ◽  
G Protein ◽  
Time Constant ◽  
Decay Time ◽  
Analytical Approach ◽  
Decay Time Constant ◽  
Afferent Neurons ◽  
Receptor Function ◽  
Vagal Afferent ◽  
G Protein Coupled

Cholecystokinin (CCK) is a gut-derived peptide that potently promotes satiety and facilitates gastric function in part by activating G protein-coupled CCK1 receptors on primary vagal afferent neurons. CCK signaling is dynamic and rapidly desensitizes, due to decreases in either receptor function and the resulting signal cascade, ion channel effectors, or both. Here we report a decay-time analytical approach using fluorescent calcium imaging that relates peak and steady-state calcium responses in dissociated vagal afferent neurons, enabling discrimination between receptor and ion channel effector functions. We found desensitization of CCK-induced activation was predictable, consistent across cells, and strongly concentration dependent. The decay-time constant (tau) was inversely proportional to CCK concentration, apparently reflecting the extent of receptor activation. To test this possibility, we directly manipulated the ion channel effector(s) with either decreased bath calcium or the broad-spectrum pore blocker ruthenium red. Conductance inhibition diminished the magnitude of the CCK responses without altering decay kinetics, confirming changes in tau reflect changes in receptor function selectively. Next, we investigated the contributions of the PKC and PKA signaling cascades on the magnitude and decay-time constants of CCK calcium responses. While inhibition of either PKC or PKA increased CCK calcium response magnitude, only general PKC inhibition significantly decreased the decay-time constant. These findings suggest that PKC alters CCK receptor signaling dynamics, while PKA alters the ion channel effector of the CCK response. This analytical approach should prove useful in understanding receptor/effector changes underlying acute desensitization of G-protein coupled signaling and provide insight into CCK receptor dynamics.

scholarly journals Measurement of Decay Time Constant of Shielding Current in ITER-TF Joint Samples

2021 ◽  
Vol 1857 (1) ◽  
pp. 012013
Author(s):  
S Imagawa ◽  
H Kajitani ◽  
T Obana ◽  
S Takada ◽  
S Hamaguchi ◽  
...  
Keyword(s):  
Time Constant ◽  
Decay Time ◽  
Decay Time Constant

Rescue of Defective G Protein-Coupled Receptor Function by Intermolecular Cooperation

2013 ◽  
pp. 239-255 ◽  
Author(s):  
Ashutosh Trehan ◽  
Kim Carol Jonas ◽  
Ilpo Huhtaniemi ◽  
Aylin Carla Hanyaloglu ◽  
Adolfo Rivero-Müller
Keyword(s):  
G Protein ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Fast, Slow, and Steady-State Effects of Contralateral Acoustic Activation of the Medial Olivocochlear Efferent System in Awake Guinea Pigs: Action of Gentamicin

1997 ◽  
Vol 78 (4) ◽  
pp. 1826-1836 ◽  
Author(s):  
Deise Lima da Costa ◽  
Anne Chibois ◽  
Jean-Paul Erre ◽  
Christophe Blanchet ◽  
RENAUD CHARLET de Sauvage ◽  
...  
Keyword(s):  
Steady State ◽  
Time Constant ◽  
Decay Time ◽  
Guinea Pigs ◽  
Round Window ◽  
Broadband Noise ◽  
Decay Time Constant ◽  
Efferent System ◽  
Medial Olivocochlear ◽  
Medial Olivocochlear Efferent System

Lima da Costa, Deise, Anne Chibois, Jean-Paul Erre, Christophe Blanchet, Renaud Charlet de Sauvage, and Jean-Marie Aran. Fast, slow, and steady-state effects of contralateral acoustic activation of the medial olivocochlear efferent system in awake guinea pigs: action of gentamicin. J. Neurophysiol. 78: 1826–1836, 1997. The function of the medial olivocochlear efferent system was observed in awake guinea pigs by recording, in the absence of ipsilateral external acoustic stimulation, the ensemble background activity (EBA) of the VIIIth nerve from an electrode chronically implanted on the round window of one ear. The EBA was measured by calculating the power value of the round window signal in the 0.5- to 2.5-kHz band after digital or analog (active) filtering. This EBA was compared with and without the addition of a low-level broadband noise to the opposite ear. The contralateral broadband noise (CLBN, 55 dB SPL) induced, via the efferent system, a decrease (suppression) of this EBA. With the use of noise bursts of different durations, two components in this suppression could be observed. After the onset of a 1-s CLBN, the power value of the EBA decreased rapidly by 38.0 ± 4.2% (mean ± SD, n = 3), with a latency of <10 ms and a decay time constant of 13.1 ± 1.0 ms (fast effect). At the offset of the 1-s CLBN, EBA came back to prestimulation values with a similar latency and a time constant of 15.5 ± 2.9 ms. During longer CLBN stimulation (≥1 min), EBA presented, after the fast decrease, an additional, slower decrease of 15.6 ± 3.1%, with a delay of 9.8 ± 1.3 s and a decay time constant of 16.1 ± 5.0 s ( n = 12, slow effect), and then remained remarkably constant for as long as observed, i.e., >2 h (steady state). The average global suppression was thus up to 47.8 ± 5.8% of the basal, pre-CLBN-stimulation EBA value. At the offset of the CLBN, EBA returned to pre-CLBN level with fast and slow phases, with, for the slow phase, no delay and a time constant of 32.1 ± 8.1 s. Fast and slow changes in EBA power values were observed after a single injection of gentamicin (GM) at different doses (150, 200, and 250 mg/kg). At 150 and 200 mg/kg, GM progressively and reversibly blocked the rapid effect, but the slow component of the efferent medial suppression remained remarkably unchanged. However, at higher doses both the fast and slow suppressions were totally yet still reversibly blocked. These observations indicate that the medial olivocochlear efferent system exerts sustained influences on outer hair cells and that this effect develops in two different steps that may have different basic cellular mechanisms.

Properties of spontaneous inhibitory synaptic currents in cultured rat spinal cord and medullary neurons

1996 ◽  
Vol 76 (1) ◽  
pp. 448-460 ◽  
Author(s):  
C. A. Lewis ◽  
D. S. Faber
Keyword(s):  
Spinal Cord ◽  
Time Constant ◽  
Decay Time ◽  
Cultured Cells ◽  
Decay Time Constant ◽  
Inhibitory Synapses ◽  
Gamma Aminobutyric Acid ◽  
Postsynaptic Receptor ◽  
Decay Times ◽  
Medullary Neurons

1. To identify the type(s) and properties of inhibitory postsynaptic receptor(s) involved in synaptic transmission in cultured rat embryonic spinal cord and medullary neurons, we have used whole cell patch-clamp techniques to record miniature inhibitory postsynaptic currents (mIPSCs) in the presence of tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. 2. The mIPSCs recorded from both spinal cord and medullary neurons had skewed amplitude distributions. 3. The glycinergic antagonist strychnine and the GABAergic antagonist bicuculline each decreased both the frequency and mean peak amplitudes of mIPSCs. We conclude that both glycine and gamma-aminobutyric acid (GABA) are neurotransmitters at inhibitory synapses in our cultured cells. 4. Most (approximately 96-97%) mIPSCs decay with single-exponential time constants, and decay time distributions were consistently best fitted by the sum of four Gaussians with decay constants as follows: D1 = 5.8 +/- 0.1 (SE) ms (n = 63), D2 = 12.2 +/- 0.2 ms (n = 61), D3 = 23.2 +/- 0.4 ms (n = 54), and D4 = 44.7 +/- 1.0 ms (n = 57). We conclude that the four classes of decay times represent kinetically different inhibitory postsynaptic receptor populations. 5. Strychnine and bicuculline usually had one of two different effects on the mIPSC decay time constant distributions; either selective decreases in the frequency of mIPSCs with decay times in certain classes (i.e., the D1 class was reduced by bicuculline, the D2 class by strychnine, and the D3 and D4 classes by both antagonists) or a nonselective depression in the frequency of mIPSCs with decay times in all four classes. The particular effect observed in a given neuron was correlated with the presence or absence of ATP and guanosine 5'-triphosphate (GTP) in the patch pipette. Namely, in 71% of the antagonist applications where the pipette contained ATP and GTP, the result was a nonselective decrease in mIPSCs in all decay time constant classes. Conversely, in 54% of the antagonist applications in their absence, the result was a selective decrease in the frequency of mIPSCs in specific decay time constant classes. 6. In some experiments, mIPSCs reappeared in antagonist solution after an essentially complete block. Recovery from block in the continued presence of antagonist was never observed in the absence of ATP and GTP (8 neurons), and, at the same time, 5 of 9 neurons patched with ATP and GTP in the pipette did show recovery (56%).

Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures

1992 ◽  
Vol 67 (6) ◽  
pp. 1698-1701 ◽  
Author(s):  
S. M. Thompson ◽  
B. H. Gahwiler
Keyword(s):  
Time Constant ◽  
Decay Time ◽  
Time Course ◽  
Hippocampal Slice ◽  
Decay Time Constant ◽  
Gabab Receptors ◽  
Gaba Uptake ◽  
Whole Cell ◽  
Synaptic Potentials ◽  
Hippocampal Slice Cultures

1. The effects of the gamma-aminobutyric acid (GABA) uptake blocker tiagabine on inhibitory synaptic potentials (IPSPs) were examined with microelectrode and whole-cell recording from CA3 pyramidal cells in rat hippocampal slice cultures. 2. Tiagabine (10-25 microM) greatly prolonged the duration of monosynaptic IPSPs elicited in the presence of excitatory amino acid antagonists but had no effect on their amplitude. Part of the prolonged time course resulted from a GABAB receptor-mediated component that was not detectable under control conditions. 3. The mean decay time constant of the underlying GABAA receptor-mediated synaptic current was increased from 16 to 250 ms. Spontaneous miniature IPSPs recorded with whole-cell clamp were unaffected by tiagabine. Pentobarbital sodium, in contrast, increased the decay time constant of both evoked and spontaneous GABAA-mediated currents. 4. Tiagabine (25 microM) inhibited spontaneous and evoked epileptiform bursting induced by increasing the extracellular potassium concentration to 8 mM. 5. We conclude that GABA uptake plays a significant role in determining the time course of evoked IPSPs and also limits the likelihood that GABAB receptors are activated.

Structural basis of G protein-coupled receptor function

1999 ◽  
Vol 151 (1-2) ◽  
pp. 181-193 ◽  
Author(s):  
Torsten Schöneberg ◽  
Günter Schultz ◽  
Thomas Gudermann
Keyword(s):  
G Protein ◽  
Structural Basis ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Enhanced Temporal Stability of Cholinergic Hippocampal Gamma Oscillations Following Respiratory Alkalosis In Vitro

2001 ◽  
Vol 85 (5) ◽  
pp. 2063-2069 ◽  
Author(s):  
Kerstin Stenkamp ◽  
J. Matias Palva ◽  
Marylka Uusisaari ◽  
Sebastian Schuchmann ◽  
Dietmar Schmitz ◽  
...  
Keyword(s):  
Time Constant ◽  
Decay Time ◽  
Oscillation Frequency ◽  
Hippocampal Slices ◽  
Temporal Stability ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Decay Time Constant ◽  
The Mean

The decrease in brain CO2 partial pressure (pCO2) that takes place both during voluntary and during pathological hyperventilation is known to induce gross alterations in cortical functions that lead to subjective sensations and altered states of consciousness. The mechanisms that mediate the effects of the decrease in pCO2 at the neuronal network level are largely unexplored. In the present work, the modulation of gamma oscillations by hypocapnia was studied in rat hippocampal slices. Field potential oscillations were induced by the cholinergic agonist carbachol under an N-methyl-D-aspartate (NMDA)-receptor blockade and were recorded in the dendritic layer of the CA3 region with parallel measurements of changes in interstitial and intraneuronal pH (pHo and pHi, respectively). Hypocapnia from 5 to 1% CO2 led to a stable monophasic increase of 0.5 and 0.2 units in pHo and pHi, respectively. The mean oscillation frequency increased slightly but significantly from 32 to 34 Hz and the mean gamma-band amplitude (20 to 80 Hz) decreased by 20%. Hypocapnia induced a dramatic enhancement of the temporal stability of the oscillations, as was indicated by a two-fold increase in the exponential decay time constant fitted to the autocorrelogram. A rise in pHi evoked by the weak base trimethylamine (TriMA) was associated with a slight increase in oscillation frequency (37 to 39 Hz) and a decrease in amplitude (30%). Temporal stability, on the other hand, was decreased by TriMA, which suggests that its enhancement in 1% CO2 was related to the rise in pHo. In 1% CO2, the decay-time constant of the evoked monosynaptic pyramidal inhibitory postsynaptic current (IPSC) was unaltered but its amplitude was enhanced. This increase in IPSC amplitude seems to significantly contribute to the enhancement of temporal stability because the enhancement was almost fully reversed by a low concentration of bicuculline. These results suggest that changes in brain pCO2 can have a strong influence on the temporal modulation of gamma rhythms.

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