Decreased excitability and voltage-gated sodium currents in aortic baroreceptor neurons contribute to the impairment of arterial baroreflex in cirrhotic rats

Lee, Choong Ku; Park, Kwang Hwa; Baik, Soon Koo; Jeong, Seong Woo

doi:10.1152/ajpregu.00129.2015

Cited by 9 publications

(6 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that BDL-induced cirrhosis alters the expression level of ion channels such as voltage-dependent Na + channels ( Lee et al, 2016 ), epithelial Na + channels ( Kim et al, 2006 ), large-conductance K Ca (BK Ca ) channels ( Yuan et al, 2016 ; Jadeja et al, 2017 ), ATP-sensitive K + channels ( Yuan et al, 2016 ), transient receptor potential canonical subfamily (TRPC) channels ( Nedungadi and Cunningham, 2014 ; Jadeja et al, 2017 ), and transient receptor potential vanilloid subfamily (TRPV) channels ( Nedungadi et al, 2012 ; Belghiti et al, 2013 ; Hong-Qian Wang et al, 2019 ). In addition, we noted the downregulation of TMEM16A (and also TMEM16F) expression in cirrhotic BDL mice, but not in non-cirrhotic PPVL mice.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

et al. 2022

View full text Add to dashboard Cite

Portal hypertension is defined as an increased pressure in the portal venous system and occurs as a major complication in chronic liver diseases. The pathological mechanism underlying the pathogenesis and development of portal hypertension has been extensively investigated. Vascular tone of portal vein smooth muscles (PVSMs) is regulated by the activities of several ion channels, including Ca2+-activated Cl− (ClCa) channels. TMEM16A is mainly responsible for ClCa channel conductance in vascular smooth muscle cells, including portal vein smooth muscle cells (PVSMCs). In the present study, the functional roles of TMEM16A channels were examined using two experimental portal hypertensive models, bile duct ligation (BDL) mice with cirrhotic portal hypertension and partial portal vein ligation (PPVL) mice with non-cirrhotic portal hypertension. Expression analyses revealed that the expression of TMEM16A was downregulated in BDL-PVSMs, but not in PPVL-PVSMs. Whole-cell ClCa currents were smaller in BDL-PVSMCs than in sham- and PPVL-PVSMCs. The amplitude of spontaneous contractions was smaller and the frequency was higher in BDL-PVSMs than in sham- and PPVL-PVSMs. Spontaneous contractions sensitive to a specific inhibitor of TMEM16A channels, T16Ainh-A01, were reduced in BDL-PVSMs. Furthermore, in normal PVSMs, the downregulation of TMEM16A expression was mimicked by the exposure to angiotensin II, but not to bilirubin. This study suggests that the activity of ClCa channels is attenuated by the downregulation of TMEM16A expression in PVSMCs associated with cirrhotic portal hypertension, which is partly mediated by increased angiotensin II in cirrhosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The physiological function of the arterial baroreflex is to normally alter heart rate and blood pressure due to arterial wall tension changes. [4] Many evidences [4,15] have showed that the arterial baroreflex baroreceptors sensed the systemic blood pressure through baroreceptor terminals innervating aortic arch and carotid sinus, and then transmitted the arterial baroreceptor afferent discharge into the dorsal medial nucleus tractus solitarii. As a result, peripheral vascular resistance, heart rate, and arterial blood pressure were subsequently decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Carotid and aortic baroreceptors sense the intraarterial blood pressure and modulate the sympathetic tone toward the opposite direction, that is, high blood pressure results in reduced sympathetic tone through baroreceptor activation, while enhanced sympathetic tone compensates for low blood pressure. [4]…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension

Chang²,

Jia³

et al. 2018

Medicine

View full text Add to dashboard Cite

This study is to investigate the effects of slow breathing on heart rate variability (HRV) and arterial baroreflex sensitivity in essential hypertension.We studied 60 patients with essential hypertension and 60 healthy controls. All subjects underwent controlled breathing at 8 and 16 breaths per minute. Electrocardiogram, respiratory, and blood pressure signals were recorded simultaneously. We studied effects of slow breathing on heart rate, blood pressure and respiratory peak, high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio of HRV with traditional and corrected spectral analysis. Besides, we tested whether slow breathing was capable of modifying baroreflex sensitivity in hypertensive subjects.Slow breathing, compared with 16 breaths per minute, decreased the heart rate and blood pressure (all P < .05), and shifted respiratory peak toward left (P < .05). Compared to 16 breaths/minute, traditional spectral analysis showed increased LF power and LF/HF ratio, decreased HF power of HRV at 8 breaths per minute (P < .05). As breathing rate decreased, corrected spectral analysis showed increased HF power, decreased LF power, LF/HF ratio of HRV (P < .05). Compared to controls, resting baroreflex sensitivity decreased in hypertensive subjects. Slow breathing increased baroreflex sensitivity in hypertensive subjects (from 59.48 ± 6.39 to 78.93 ± 5.04 ms/mm Hg, P < .05) and controls (from 88.49 ± 6.01 to 112.91 ± 7.29 ms/mm Hg, P < .05).Slow breathing can increase HF power and decrease LF power and LF/HF ratio in essential hypertension. Besides, slow breathing increased baroreflex sensitivity in hypertensive subjects. These demonstrate slow breathing is indeed capable of shifting sympatho-vagal balance toward vagal activities and increasing baroreflex sensitivity, suggesting a safe, therapeutic approach for essential hypertension.

show abstract

“…Recent studies have highlighted that sympathetic SGCs play critical roles in the physiological regulation of neuronal metabolism and survival, cell excitability, synaptic transmission, and overall sympathetic output [ 3 , 4 ]. Previous studies showed that certain pathological conditions including chronic heart failure [ 5 ], cirrhosis [ 6 ], and traumatic brain injury [ 7 ] cause autonomic imbalance due to sympathetic overactivity. However, the involvement of SGCs in the cellular mechanisms underlying abnormal sympathetic output remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia

Kim,

Kang,

Nguyen

et al. 2024

Korean J Physiol Pharmacol

Self Cite

View full text Add to dashboard Cite

Satellite glial cells (SGCs), a major type of glial cell in the autonomic ganglia, closely envelop the cell body and even the synaptic regions of a single neuron with a very narrow gap. This structurally unique organization suggests that autonomic neurons and SGCs may communicate reciprocally. Glial Ca 2+ signaling is critical for controlling neural activity. Here, for the first time we identified the machinery of store-operated Ca 2+ entry (SOCE) which is critical for cellular Ca 2+ homeostasis in rat sympathetic ganglia under normal and pathological states. Quantitative real-time PCR and immunostaining analyses showed that Orai1 and stromal interaction molecules 1 (STIM1) proteins are the primary components of SOCE machinery in the sympathetic ganglia. When the internal Ca 2+ stores were depleted in the absence of extracellular Ca 2+ , the number of plasmalemmal Orai1 puncta was increased in neurons and SGCs, suggesting activation of the Ca 2+ entry channels. Intracellular Ca 2+ imaging revealed that SOCE was present in SGCs and neurons; however, the magnitude of SOCE was much larger in the SGCs than in the neurons. The SOCE was significantly suppressed by GSK7975A, a selective Orai1 blocker, and Pyr6, a SOCE blocker. Lipopolysaccharide (LPS) upregulated the glial fibrillary acidic protein and Toll-like receptor 4 in the sympathetic ganglia. Importantly, LPS attenuated SOCE via downregulating Orai1 and STIM1 expression. In conclusion, sympathetic SGCs functionally express the SOCE machinery, which is indispensable for intracellular Ca 2+ signaling. The SOCE is highly susceptible to inflammation, which may affect sympathetic neuronal activity and thereby autonomic output.

show abstract

Decreased excitability and voltage-gated sodium currents in aortic baroreceptor neurons contribute to the impairment of arterial baroreflex in cirrhotic rats

Cited by 9 publications

References 77 publications

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

Effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension

Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia

Contact Info

Product

Resources

About