scholarly journals TRPV1 channels contribute to spontaneous glutamate release in nucleus tractus solitarii following chronic intermittent hypoxia

2019 ◽  
Vol 121 (3) ◽  
pp. 881-892 ◽  
Author(s):  
David D. Kline ◽  
Sheng Wang ◽  
Diana L. Kunze
Keyword(s):  
Synaptic Transmission ◽  
Intermittent Hypoxia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nucleus Tractus Solitarii ◽  
Chronic Intermittent Hypoxia ◽  
Excitatory Postsynaptic Currents ◽  
Epsc Amplitude ◽  
Postsynaptic Currents ◽  
Transient Receptor

Chronic intermittent hypoxia (CIH) reduces afferent-evoked excitatory postsynaptic currents (EPSCs) but enhances basal spontaneous (s) and asynchronous (a) EPSCs in second-order neurons of nucleus tractus solitarii (nTS), a major area for cardiorespiratory control. The net result is an increase in synaptic transmission. The mechanisms by which this occurs are unknown. The N-type calcium channel and transient receptor potential cation channel TRPV1 play prominent roles in nTS sEPSCs and aEPSCs. The functional role of these channels in CIH-mediated afferent-evoked EPSC, sEPSC, and aEPSC was tested in rat nTS slices following antagonist inhibition and in mouse nTS slices that lack TRPV1. Block of N-type channels decreased aEPSCs in normoxic and, to a lesser extent, CIH-exposed rats. sEPSCs examined in the presence of TTX (miniature EPSCs) were also decreased by N-type block in normoxic but not CIH-exposed rats. Antagonist inhibition of TRPV1 reduced the normoxic and the CIH-mediated increase in sEPSCs, aEPSCs, and mEPSCs. As in rats, in TRPV1+/+ control mice, aEPSCs, sEPSCs, and mEPSCs were enhanced following CIH. However, none were enhanced in TRPV1−/− null mice. Normoxic tractus solitarii (TS)-evoked EPSC amplitude, and the decrease after CIH, were comparable in control and null mice. In rats, TRPV1 was localized in the nodose-petrosal ganglia (NPG) and their central branches. CIH did not alter TRPV1 mRNA but increased its protein in NPG consistent with an increased contribution of TRPV1. Together, our studies indicate TRPV1 contributes to the CIH increase in aEPSCs and mEPSCs, but the CIH reduction in TS-EPSC amplitude occurs via an alternative mechanism. NEW & NOTEWORTHY This study provides information on the underlying mechanisms responsible for the chronic intermittent hypoxia (CIH) increase in synaptic transmission that leads to exaggerated sympathetic nervous and respiratory activity at baseline and in response to low oxygen. We demonstrate that the CIH increase in asynchronous and spontaneous excitatory postsynaptic currents (EPSCs) and miniature EPSCs, but not decrease in afferent-driven EPSCs, is dependent on transient receptor potential vanilloid type 1 (TRPV1). Thus TRPV1 is important in controlling nucleus tractus solitarii synaptic activity during CIH.

scholarly journals Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats

2019 ◽  
Vol 130 (4) ◽  
pp. 592-608 ◽  
Author(s):  
Danielle M. Gregor ◽  
Wanhong Zuo ◽  
Rao Fu ◽  
Alex Bekker ◽  
Jiang-Hong Ye
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ethanol Withdrawal ◽  
Transient Receptor Potential Vanilloid ◽  
Glutamatergic Transmission ◽  
Lateral Habenula ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Transient Receptor ◽  
Spontaneous Excitatory Postsynaptic Currents

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Recent rat studies indicate that alcohol withdrawal can trigger a negative emotional state including anxiety- and depression-like behaviors and hyperalgesia, as well as elevated glutamatergic transmission and activity in lateral habenula neurons. TRPV1, a vanilloid receptor expressed in the habenula, is involved in pain, alcohol dependence, and glutamatergic transmission. The authors therefore hypothesized that TRPV1 contributes to the changes in both the behavioral phenotypes and the habenula activity in alcohol-withdrawn rats. Methods Adult male Long-Evans rats (n = 110 and 280 for electrophysiology and behaviors, respectively), randomly assigned into the alcohol and water (Naïve) groups, were trained to consume either alcohol or water-only using an intermittent-access procedure. Slice electrophysiology was used to measure spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons. The primary outcome was the change in alcohol-related behaviors and lateral habenula activity induced by pharmacologic manipulation of TRPV1 activity. Results The basal frequency of spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons in alcohol-withdrawn rats was significantly increased. The TRPV1 antagonist capsazepine (10 µM) induced a stronger inhibition on spontaneous excitatory postsynaptic currents (mean ± SD; by 26.1 ± 27.9% [n = 11] vs. 6.7 ± 18.6% [n = 17], P = 0.027) and firing (by 23.4 ± 17.6% [n = 9] vs. 11.9 ± 16.3% [n = 12], P = 0.025) in Withdrawn rats than Naive rats. By contrast, the TRPV1 agonist capsaicin (3 μM) produced a weaker potentiation in Withdrawn than Naïve rats (spontaneous excitatory postsynaptic currents: by 203.6 ± 124.7% [n = 20] vs. 415.2 ± 424.3% [n = 15], P < 0.001; firing: 38.1 ± 14.7% [n = 11] vs. 73.9 ± 41.9% [n = 11], P < 0.001). Conversely, capsaicin’s actions in Naïve but not in Withdrawn rats were significantly attenuated by the pretreatment of TRPV1 endogenous agonist N-Oleoyldopamine. In Withdrawn rats, intra-habenula infusion of TRPV1 antagonists attenuated hyperalgesia and anxiety-like behaviors, decreased alcohol consumption upon resuming drinking, and elicited a conditioned place preference. Conclusions Enhanced TRPV1 function may contribute to increased glutamatergic transmission and activity of lateral habenula neurons, resulting in the aberrant behaviors during ethanol withdrawal.

Chronic intermittent hypoxia impairs diuretic and natriuretic responses to volume expansion in rats with preserved low-pressure baroreflex control of the kidney

2021 ◽  
Vol 320 (1) ◽  
pp. F1-F16
Author(s):  
Sara AlMarabeh ◽  
Julie O’Neill ◽  
Jeremy Cavers ◽  
Eric F. Lucking ◽  
Ken D. O’Halloran ◽  
...  
Keyword(s):  
High Pressure ◽  
Volume Expansion ◽  
Intermittent Hypoxia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Low Pressure ◽  
Chronic Intermittent Hypoxia ◽  
Transient Receptor Potential Vanilloid ◽  
Baroreflex Control ◽  
Obstructive Sleep

We examined the effects of exposure to chronic intermittent hypoxia (CIH) on baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory responses to volume expansion (VE) before and after intrarenal transient receptor potential vanilloid 1 (TRPV1) blockade by capsaizepine (CPZ). Male Wistar rats were exposed to 96 cycles of hypoxia per day for 14 days (CIH) or normoxia. Urine flow and absolute Na+ excretion during VE were less in CIH-exposed rats, but the progressive decrease in RSNA during VE was preserved. Assessment of the high-pressure baroreflex revealed an increase in the operating and response range of RSNA and decreased slope in CIH-exposed rats with substantial hypertension [+19 mmHg basal mean arterial pressure (MAP)] but not in a second cohort with modest hypertension (+12 mmHg). Intrarenal CPZ caused diuresis, natriuresis, and a reduction in MAP in sham-exposed (sham) and CIH-exposed rats. After intrarenal CPZ, diuretic and natriuretic responses to VE in CIH-exposed rats were equivalent to those of sham rats. TRPV1 expression in the renal pelvic wall was similar in both experimental groups. Exposure to CIH did not elicit glomerular hypertrophy, renal inflammation, or oxidative stress. We conclude that exposure to CIH 1) does not impair the low-pressure baroreflex control of RSNA; 2) has modest effects on the high-pressure baroreflex control of RSNA, most likely indirectly due to hypertension; 3) can elicit hypertension in the absence of kidney injury; and 4) impairs diuretic and natriuretic responses to fluid overload. Our results suggest that exposure to CIH causes renal dysfunction, which may be relevant to obstructive sleep apnea.

scholarly journals Brain-derived Neurotrophic Factor (BDNF)-induced Mitochondrial Motility Arrest and Presynaptic Docking Contribute to BDNF-enhanced Synaptic Transmission

2013 ◽  
Vol 289 (3) ◽  
pp. 1213-1226 ◽  
Author(s):  
Bo Su ◽  
Yun-Song Ji ◽  
Xu-lu Sun ◽  
Xiang-Hua Liu ◽  
Zhe-Yu Chen
Keyword(s):  
Synaptic Transmission ◽  
Neurotrophic Factor ◽  
Hippocampal Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Brain Derived Neurotrophic Factor ◽  
High Energy ◽  
Mitochondrial Transport ◽  
Mitochondrial Motility ◽  
Transient Receptor

Appropriate mitochondrial transport and distribution are essential for neurons because of the high energy and Ca2+ buffering requirements at synapses. Brain-derived neurotrophic factor (BDNF) plays an essential role in regulating synaptic transmission and plasticity. However, whether and how BDNF can regulate mitochondrial transport and distribution are still unclear. Here, we find that in cultured hippocampal neurons, application of BDNF for 15 min decreased the percentage of moving mitochondria in axons, a process dependent on the activation of the TrkB receptor and its downstream PI3K and phospholipase-Cγ signaling pathways. Moreover, the BDNF-induced mitochondrial stopping requires the activation of transient receptor potential canonical 3 and 6 (TRPC3 and TRPC6) channels and elevated intracellular Ca2+ levels. The Ca2+ sensor Miro1 plays an important role in this process. Finally, the BDNF-induced mitochondrial stopping leads to the accumulation of more mitochondria at presynaptic sites. Mutant Miro1 lacking the ability to bind Ca2+ prevents BDNF-induced mitochondrial presynaptic accumulation and synaptic transmission, suggesting that Miro1-mediated mitochondrial motility is involved in BDNF-induced mitochondrial presynaptic docking and neurotransmission. Together, these data suggest that mitochondrial transport and distribution play essential roles in BDNF-mediated synaptic transmission.

scholarly journals The Absence of the Transient Receptor Potential Vanilloid 1 Directly Impacts on the Expression and Localization of the Endocannabinoid System in the Mouse Hippocampus

2021 ◽  
Vol 15 ◽  
Author(s):  
Jon Egaña-Huguet ◽  
Itziar Bonilla-Del Río ◽  
Sonia M. Gómez-Urquijo ◽  
Amaia Mimenza ◽  
Miquel Saumell-Esnaola ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Transient Receptor Potential ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Perforant Path ◽  
Transient Receptor Potential Vanilloid ◽  
Excitatory Synapses ◽  
Selective Ligand ◽  
Transient Receptor

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective ligand-gated cation channel involved in synaptic transmission, plasticity, and brain pathology. In the hippocampal dentate gyrus, TRPV1 localizes to dendritic spines and dendrites postsynaptic to excitatory synapses in the molecular layer (ML). At these same synapses, the cannabinoid CB1 receptor (CB1R) activated by exogenous and endogenous cannabinoids localizes to the presynaptic terminals. Hence, as both receptors are activated by endogenous anandamide, co-localize, and mediate long-term depression of the excitatory synaptic transmission at the medial perforant path (MPP) excitatory synapses though by different mechanisms, it is plausible that they might be exerting a reciprocal influence from their opposite synaptic sites. In this anatomical scenario, we tested whether the absence of TRPV1 affects the endocannabinoid system. The results obtained using biochemical techniques and immunoelectron microscopy in a mouse with the genetic deletion of TRPV1 show that the expression and localization of components of the endocannabinoid system, included CB1R, change upon the constitutive absence of TRPV1. Thus, the expression of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) drastically increased in TRPV1−/− whole homogenates. Furthermore, CB1R and MAGL decreased and the cannabinoid receptor interacting protein 1a (CRIP1a) increased in TRPV1−/− synaptosomes. Also, CB1R positive excitatory terminals increased, the number of excitatory terminals decreased, and CB1R particles dropped significantly in inhibitory terminals in the dentate ML of TRPV1−/− mice. In the outer 2/3 ML of the TRPV1−/− mutants, the proportion of CB1R particles decreased in dendrites, and increased in excitatory terminals and astrocytes. In the inner 1/3 ML, the proportion of labeling increased in excitatory terminals, neuronal mitochondria, and dendrites. Altogether, these observations indicate the existence of compensatory changes in the endocannabinoid system upon TRPV1 removal, and endorse the importance of the potential functional adaptations derived from the lack of TRPV1 in the mouse brain.

scholarly journals A Transient Receptor Potential-Like Channel Mediates Synaptic Transmission in Rod Bipolar Cells

2009 ◽  
Vol 29 (19) ◽  
pp. 6088-6093 ◽  
Author(s):  
Y. Shen ◽  
J. A. Heimel ◽  
M. Kamermans ◽  
N. S. Peachey ◽  
R. G. Gregg ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Bipolar Cells ◽  
Transient Receptor ◽  
Rod Bipolar Cells
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