Coordinated Regulation of Vascular Ca2+ and K+ Channels by Integrin Signaling

Gui, Peichun; Chao, Jun-Tzu; Wu, Xin; Yang, Yan; Davis, George E.; Davis, Michael J.

doi:10.1007/978-1-4419-6066-5_7

Cited by 30 publications

(34 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Blockade of RyRs inhibited integrin-mediated myogenic constriction of afferent arterioles (FIGURE 8) (64). RyR-dependent Ca 2ϩ signaling was independent of Ca 2ϩ entry via L-type VOCCs in the renal (214), but not in nonrenal vessels (525). Ca 2ϩ -induced Ca 2ϩ release in the afferent arteriole may be more critical in the initiation of the myogenic response than in the sustained phase when Ca 2ϩ entry through VOCCs is essential.…”

Section: A Integrinsmentioning

confidence: 98%

“…VSMCs exhibit heterogeneity in BK Ca activity or their sensitivity that may contribute to tissue-specific differences in the regulation of myogenic vasoconstriction (525,618,1632). For example, the BK Ca is more sensitive to increased [Ca 2ϩ ] i resulting from Ca 2ϩ sparks generated by Ca 2ϩ release from sarcoplasmic reticulum in cerebral than skeletal muscle cremaster arteries.…”

Section: B Potassium Channelsmentioning

confidence: 98%

“…Thus both VOCCs that excite the myogenic response and BK channels that generally inhibit the response are under constitutive control by an interaction between ␣ 5 ␤ 1 integrins and fibronectins. The balance of their activities could determine the degree of pressure-induced myogenic tone and perhaps vascular remodeling (525).…”

Section: A Integrinsmentioning

confidence: 99%

See 2 more Smart Citations

Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

380

383

View full text Add to dashboard Cite

Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca(2+)]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca(2+)]i occurs predominantly by Ca(2+) influx through L-type voltage-operated Ca(2+) channels (VOCC). Increased [Ca(2+)]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca(2+) from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca(2+) sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

show abstract

Section: A Integrinsmentioning

confidence: 98%

Section: B Potassium Channelsmentioning

confidence: 98%

See 1 more Smart Citation

Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

380

383

View full text Add to dashboard Cite

show abstract

“…In the renal circulation, pressure-induced myogenic constriction in the afferent arteriole is an important protective mechanism to prevent the transmission of elevated systemic pressure to the glomerular capillaries, a critical determinant in the progression of glomerulosclerosis in diabetes, hypertension, and end-stage renal disease. However, the mechanisms that transduce the changes in perfusion pressure into vascular smooth muscle cells (VSMCs) to initiate myogenic constriction are still elusive (7,15,17,28). Many studies on mechanotransduction of myogenic response have focused on the mechanosensitive gating of stretch-sensitive channels in triggering membrane depolarization and Ca 2ϩ influx.…”

mentioning

confidence: 99%

Remanent cell traction force in renal vascular smooth muscle cells induced by integrin-mediated mechanotransduction

Balasubramanian

Sham

et al. 2013

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

It was previously demonstrated in isolated renal vascular smooth muscle cells (VSMCs) that integrin-mediated mechanotransduction triggers intracellular Ca(2+) mobilization, which is the hallmark of myogenic response in VSMCs. To test directly whether integrin-mediated mechanotransduction results in the myogenic response-like behavior in renal VSMCs, cell traction force microscopy was used to monitor cell traction force when the cells were pulled with fibronectin-coated or low density lipoprotein (LDL)-coated paramagnetic beads. LDL-coated beads were used as a control for nonintegrin-mediated mechanotransduction. Pulling with LDL-coated beads increased the cell traction force by 61 ± 12% (9 cells), which returned to the prepull level after the pulling process was terminated. Pulling with noncoated beads had a minimal increase in the cell traction force (12 ± 9%, 8 cells). Pulling with fibronectin-coated beads increased the cell traction force by 56 ± 20% (7 cells). However, the cell traction force was still elevated by 23 ± 14% after the pulling process was terminated. This behavior is analogous to the changes of vascular resistance in pressure-induced myogenic response, in which vascular resistance remains elevated after myogenic constriction. Fibronectin is a native ligand for α(5)β(1)-integrins in VSMCs. Similar remanent cell traction force was found when cells were pulled with beads coated with β(1)-integrin antibody (Ha2/5). Activation of β(1)-integrin with soluble antibody also triggered variations of cell traction force and Ca(2+) mobilization, which were abolished by the Src inhibitor. In conclusion, mechanical force transduced by α(5)β(1)-integrins triggered a myogenic response-like behavior in isolated renal VSMCs.

show abstract

“…Indeed, multiscale modeling that spans processes ranging from the subcellular up to the organ level is required to elucidate clinical and experimental findings such as the effects of integrins [31,32], epithelial sodium channels (ENaCs) [33,34], angiotensin II (AngII) [35][36][37][38], nitric oxide (NO) [39,40], and an array of other vasomodulators [41][42][43][44], or the pathophysiology associated with certain chronic conditions such as hypertension [45,46], diabetes mellitus [47,48], or chronic kidney disease [49,50]. Most of these previous studies have used simple compartmental models (Windkessels), ordinary or partial differential equations, and more recently, probabilistic methods for reproducing renal vascular networks [28].…”

Section: Introductionmentioning

confidence: 99%

A Multicellular Vascular Model of the Renal Myogenic Response

2018

View full text Add to dashboard Cite

Abstract:The myogenic response is a key autoregulatory mechanism in the mammalian kidney. Triggered by blood pressure perturbations, it is well established that the myogenic response is initiated in the renal afferent arteriole and mediated by alterations in muscle tone and vascular diameter that counterbalance hemodynamic perturbations. The entire process involves several subcellular, cellular, and vascular mechanisms whose interactions remain poorly understood. Here, we model and investigate the myogenic response of a multicellular segment of an afferent arteriole. Extending existing work, we focus on providing an accurate-but still computationally tractable-representation of the coupling among the involved levels. For individual muscle cells, we include detailed Ca 2+ signaling, transmembrane transport of ions, kinetics of myosin light chain phosphorylation, and contraction mechanics. Intercellular interactions are mediated by gap junctions between muscle or endothelial cells. Additional interactions are mediated by hemodynamics. Simulations of time-independent pressure changes reveal regular vasoresponses throughout the model segment and stabilization of a physiological range of blood pressures (80-180 mmHg) in agreement with other modeling and experimental studies that assess steady autoregulation. Simulations of time-dependent perturbations reveal irregular vasoresponses and complex dynamics that may contribute to the complexity of dynamic autoregulation observed in vivo. The ability of the developed model to represent the myogenic response in a multiscale and realistic fashion, under feasible computational load, suggests that it can be incorporated as a key component into larger models of integrated renal hemodynamic regulation.

show abstract

Coordinated Regulation of Vascular Ca2+ and K+ Channels by Integrin Signaling

Cited by 30 publications

References 56 publications

Renal Autoregulation in Health and Disease

Renal Autoregulation in Health and Disease

Remanent cell traction force in renal vascular smooth muscle cells induced by integrin-mediated mechanotransduction

A Multicellular Vascular Model of the Renal Myogenic Response

Contact Info

Product

Resources

About