scholarly journals Effects of TRPC6 Inactivation on Glomerulosclerosis and Renal Fibrosis in Aging Rats

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 856
Author(s):  
Eun Young Kim ◽  
Stuart E. Dryer
Keyword(s):  
Renal Function ◽  
Protective Effect ◽  
Renal Fibrosis ◽  
Transient Receptor Potential ◽  
Smooth Muscle Actin ◽  
Receptor Potential ◽  
Sprague Dawley ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
Transient Receptor

Canonical transient receptor potential 6 (TRPC6) channels have been implicated in familial and acquired forms of focal and segmental glomerulosclerosis (FSGS) in patients and animal models, as well as in renal fibrosis following ureteral obstruction in mice. Aging also evokes declines in renal function owing to effects on almost every renal compartment in humans and rodents. Here, we have examined the role of TRPC6 in driving inflammation and fibrosis during aging in Sprague-Dawley rats. This was assessed in rats with non-functional TRPC6 channels owing to CRISPR-Cas9 deletion of a portion of the ankyrin repeat domain required for the assembly of functional TRPC6 channels (Trpc6del/del rats). Wild-type littermates (Trpc6wt/wt rats) were used as controls. Animals were evaluated at 2 months and 12 months of age. There was no sign of kidney disease at 2 months of age, regardless of genotype. However, by 12 months of age, all rats examined showed declines in renal function associated with albuminuria, azotemia and increased urine excretion of β2–microglobulin, a marker for proximal tubule pathology. These changes were equally severe in Trpc6wt/wt and Trpc6del/del rats. We also observed age-related increases in renal cortical expression of markers of fibrosis (α-smooth muscle actin and vimentin) and inflammation (NLRP3 and pro-IL−1β), and there was no detectable protective effect of TRPC6 inactivation. Tubulointerstitial fibrosis assessed from histology also appeared equally severe in Trpc6wt/wt and Trpc6del/del rats. By contrast, glomerular pathology, blindly scored from histological sections, suggested a significant protective effect of TRPC6 inactivation, but only within the glomerular compartment.

scholarly journals Functional Interaction among KCa and TRP Channels for Cardiovascular Physiology: Modern Perspectives on Aging and Chronic Disease

2019 ◽  
Vol 20 (6) ◽  
pp. 1380 ◽  
Author(s):  
Erik Behringer ◽  
Md Hakim
Keyword(s):  
Blood Flow ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
The Body ◽  
Cardiovascular Physiology ◽  
Treatment And Prevention ◽  
Kca Channels ◽  
Age Related ◽  
Transient Receptor

Effective delivery of oxygen and essential nutrients to vital organs and tissues throughout the body requires adequate blood flow supplied through resistance vessels. The intimate relationship between intracellular calcium ([Ca2+]i) and regulation of membrane potential (Vm) is indispensable for maintaining blood flow regulation. In particular, Ca2+-activated K+ (KCa) channels were ascertained as transducers of elevated [Ca2+]i signals into hyperpolarization of Vm as a pathway for decreasing vascular resistance, thereby enhancing blood flow. Recent evidence also supports the reverse role for KCa channels, in which they facilitate Ca2+ influx into the cell interior through open non-selective cation (e.g., transient receptor potential; TRP) channels in accord with robust electrical (hyperpolarization) and concentration (~20,000-fold) transmembrane gradients for Ca2+. Such an arrangement supports a feed-forward activation of Vm hyperpolarization while potentially boosting production of nitric oxide. Furthermore, in vascular types expressing TRP channels but deficient in functional KCa channels (e.g., collecting lymphatic endothelium), there are profound alterations such as downstream depolarizing ionic fluxes and the absence of dynamic hyperpolarizing events. Altogether, this review is a refined set of evidence-based perspectives focused on the role of the endothelial KCa and TRP channels throughout multiple experimental animal models and vascular types. We discuss the diverse interactions among KCa and TRP channels to integrate Ca2+, oxidative, and electrical signaling in the context of cardiovascular physiology and pathology. Building from a foundation of cellular biophysical data throughout a wide and diverse compilation of significant discoveries, a translational narrative is provided for readers toward the treatment and prevention of chronic, age-related cardiovascular disease.

scholarly journals Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis

2019 ◽  
Vol 8 (12) ◽  
pp. 2187 ◽  
Author(s):  
Chung-Kuan Wu ◽  
Chia-Lin Wu ◽  
Tzu-Cheng Su ◽  
Yu Ru Kou ◽  
Chew-Teng Kor ◽  
...  
Keyword(s):  
Renal Function ◽  
Acute Tubular Necrosis ◽  
Transient Receptor Potential ◽  
Kidney Injury ◽  
Receptor Potential ◽  
Total Recovery ◽  
Tubular Necrosis ◽  
Kaplan Meier ◽  
Transient Receptor ◽  
Renal Tubular

Background: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca2+-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive. Methods: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan–Meier curves and logistic regression analysis. Results: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35–37.75; p = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26–37.27; p = 0.03). Conclusion: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted.

Effect of Nicotine on Chorda Tympani Responses to Salty and Sour Stimuli

2007 ◽  
Vol 98 (3) ◽  
pp. 1662-1674 ◽  
Author(s):  
Vijay Lyall ◽  
Tam-Hao T. Phan ◽  
Shobha Mummalaneni ◽  
Mahdis Mansouri ◽  
Gerard L. Heck ◽  
...  
Keyword(s):  
Elevated Temperature ◽  
Transient Receptor Potential ◽  
Taste Receptor ◽  
Direct Interaction ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Chorda Tympani ◽  
Sprague Dawley ◽  
Maximum Enhancement ◽  
Transient Receptor

The effect of nicotine on the benzamil (Bz)-insensitive (transient receptor potential vanilloid-1 variant cation channel, TRPV1t) and the Bz-sensitive (epithelial Na+ channel, ENaC) salt taste receptors and sour taste was investigated by monitoring intracellular Na+ and H+ activity (pHi) in polarized fungiform taste receptor cells (TRCs) and the chorda tympani (CT) nerve responses to NaCl, KCl, and HCl. CT responses in Sprague–Dawley rats and both wildtype and TRPV1 knockout (KO) mice were recorded in the presence and absence of agonists [resiniferatoxin (RTX) and elevated temperature] and an antagonist (SB-366791) of TRPV1t, the ENaC blocker (Bz), and varying apical pH (pHo). At concentrations <0.015 M, nicotine enhanced and at >0.015 M, it inhibited CT responses to KCl and NaCl. Nicotine produced maximum enhancement in the Bz-insensitive NaCl CT response at pHo between 6 and 7. RTX and elevated temperature increased the sensitivity of the CT response to nicotine in salt-containing media, and SB-366791 inhibited these effects. TRPV1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to nicotine, RTX, and elevated temperature. We conclude that nicotine modulates salt responses by direct interaction with TRPV1t. At pHo >8, the apical membrane permeability of nicotine was increased significantly, resulting in increase in TRC pHi and volume, activation of ENaC, and enhancement of the Bz-sensitive NaCl CT response. At pHo >8, nicotine also inhibited the phasic component of the HCl CT response. We conclude that the effects of nicotine on ENaC and the phasic HCl CT response arise from increases in TRC pHi and volume.

scholarly journals Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis

2014 ◽  
Vol 26 (8) ◽  
pp. 1855-1876 ◽  
Author(s):  
Youakim Saliba ◽  
Ralph Karam ◽  
Viviane Smayra ◽  
Georges Aftimos ◽  
Joel Abramowitz ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Canonical ◽  
Transient Receptor

scholarly journals TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

2013 ◽  
Vol 305 (1) ◽  
pp. G106-G117 ◽  
Author(s):  
ZuoJun Ren ◽  
Mee-Ra Rhyu ◽  
Tam-Hao T. Phan ◽  
Shobha Mummalaneni ◽  
Karnam S. Murthy ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Sweet Taste ◽  
Triphenylphosphine Oxide ◽  
Chorda Tympani ◽  
Sprague Dawley ◽  
Nerve Response ◽  
Fat Taste ◽  
Transient Receptor ◽  
The Relationship

Transient receptor potential (TRP) subfamily M member 5 (TRPM5) cation channel is involved in sensing sweet, bitter, umami, and fat taste stimuli, complex-tasting divalent salts, and temperature-induced changes in sweet taste. To investigate if the amiloride- and benzamil (Bz)-insensitive NaCl chorda tympani (CT) taste nerve response is also regulated in part by TRPM5, CT responses to 100 mM NaCl + 5 μM Bz (NaCl + Bz) were monitored in Sprague-Dawley rats, wild-type (WT) mice, and TRP vanilloid subfamily member 1 (TRPV1) and TRPM5 knockout (KO) mice in the presence of resiniferatoxin (RTX), a TRPV1 agonist. In rats, NaCl + Bz + RTX CT responses were also monitored in the presence of triphenylphosphine oxide, a specific TRPM5 blocker, and capsazepine and N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791), specific TRPV1 blockers. In rats and WT mice, RTX produced biphasic effects on the NaCl + Bz CT response, enhancing the response at 0.5–1 μM and inhibiting it at >1 μM. The NaCl + Bz + SB-366791 CT response in rats and WT mice and the NaCl + Bz CT response in TRPV1 KO mice were inhibited to baseline level and were RTX-insensitive. In rats, blocking TRPV1 by capsazepine or TRPM5 by triphenylphosphine oxide inhibited the tonic NaCl + Bz CT response and shifted the relationship between RTX concentration and the magnitude of the tonic CT response to higher RTX concentrations. TRPM5 KO mice elicited no constitutive NaCl + Bz tonic CT response. The relationship between RTX concentration and the magnitude of the tonic NaCl + Bz CT response was significantly attenuated and shifted to higher RTX concentrations. The results suggest that pharmacological or genetic alteration of TRPM5 activity modulates the Bz-insensitive NaCl CT response and its modulation by TRPV1 agonists.

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