Electrophysiological effects of endothelin‐1 and their relationship to contraction in rat renal arterial smooth muscle

Betts, Luisa C; Kozlowski, Roland Z.

doi:10.1038/sj.bjp.0703377

Cited by 35 publications

(24 citation statements)

References 46 publications

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“…This result is essentially consistent with previous reports in vivo and in vitro in that the nifedipine partially reverses the renal vasoconstrictor effect of ET-1 [30,40]. Furthermore, it has been reported in the renal artery that ET-1 induces membrane depolarization, and this effect is likely to favor L-type Ca 2+ activity, allowing Ca 2+ influx necessary for contraction [41]. However, several researchers have shown that the contraction induced by ET-1 is resistant to nifedipine [42][43][44][45].…”

Section: Discussionsupporting

confidence: 82%

Mechanisms Underlying the Contractile Response to Endothelin-1 in the Rat Renal Artery

Callera¹,

Bendhack²

2003

Pharmacology

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We assessed the functional response and the mechanisms following receptor stimulation of endothelin-1 (ET-1) in the rat renal artery. In this study, isometric tension was recorded in renal artery rings without endothelium. Cumulative application of ET-1 from 0.1 to 100 nmol/l induced a sustained concentration-dependent contraction in the renal artery. Submaximal contraction induced by 10 nmol/l ET-1 in 2.5 mmol/l Ca²⁺ and in the absence of inhibitors was used as control response (100%). The relative contribution of different sources of Ca²⁺ in ET-1-induced contraction was evaluated. The contractile response to 10 nmol/l ET-1 in 2.5 mmol/l Ca²⁺(1.2 ± 0.2 g) was significantly inhibited either in Ca²⁺-free solution containing 100 µmol/l ethylene glycol bis-(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (0.6 ± 0.1 g) or after depletion of intracellular Ca²⁺ stores (0.62 ± 0.05 g). The contribution of phospholipase C and protein kinase C was evaluated by using their inhibitors 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC) and [1-(5-isoquinolinesulfonyl)-2-methylpiperazine] (H-7), respectively. The contractile response to 10 nmol/l ET-1 was inhibited by 10 µmol/l NCDC (to 80 ± 6%) and 30 µmol/l H-7 (to 76.6 ± 6.5%). We found that 1 µmol/l nifedipine inhibited the ET-1-induced contraction (to 48.7 ± 6.9%), indicating the contribution of Ca²⁺ influx through voltage-gated L-type Ca²⁺ channels to this response. Further, the inhibitory effect of nifedipine was to a greater extent as compared with NCDC or H-7. Additive inhibition of ET-1-induced contraction was not observed in the presence of both nifedipine and NCDC. We also evaluated the role of the ionic transport system in the ET-1-induced response by using 20 nmol/l 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an inhibitor of Na⁺-H⁺ exchange, or 100 µmol/l ouabain, an inhibitor of Na⁺-K⁺-ATPase. The response to ET-1 was decreased by both EIPA (to 61.6 ± 8.4%) and ouabain (to 62.1 ± 8.6%). The contribution of Na⁺-Ca²⁺ exchange to ouabain action was tested using the inhibitor dimethyl amiloride HCl (10 µmol/l). The decrease in ET-1-induced contraction by the combination of ouabain and dimethyl amiloride HCl was similar to that observed with ouabain alone. In view of these observations, both extra- and intracellular sources of Ca²⁺ contribute to the contractile response induced by ET-1 in the renal artery. Our findings also revealed the importance of Ca²⁺ influx through voltage-gated L-type Ca²⁺ channels in mediating contraction to ET-1 in the renal artery, whereas a minor role of phospholipase C and protein kinase C was observed. Na⁺-H⁺ exchange and Na⁺-K⁺-ATPase also play a role in the ET-1-induced contraction in renal artery. Moreover, the contribution of Na⁺-K⁺-ATPase in ET-1 contraction is not an Na⁺-Ca²⁺

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Section: Discussionsupporting

confidence: 82%

Mechanisms Underlying the Contractile Response to Endothelin-1 in the Rat Renal Artery

Callera¹,

Bendhack²

2003

Pharmacology

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“…One possible reason for this discrepancy in the K ϩ ionic dependency of adipocyte Vm, is that in our study isolated adipocytes were clearly identified as such, whereas in previous studies of the ionic dependency of Vm sharp electrodes were impaled blindly into white fat explants, where it was assumed that Vm was recorded from adipocytes. This is a pertinent point, since only a narrow band of cytoplasm circumnavigates the lipid droplet (11,49), whereas other cells of the adipose tissue, such as smooth muscle and endothelia of its vasculature, being larger, have a higher likelihood of actual impalement and have Vm values quite similar to those reported for identified adipocytes; for example, the resting membrane potential of smooth muscle myocytes from a variety of arterial tissues range from Ϫ32 mV in pulmonary (3) to Ϫ39 mV in renal (8), whereas the resting Vm for endothelial cells range from Ϫ26 mV from pulmonary artery (52) to Ϫ43 mV from aorta (9). Another possible reason for this discrepancy is that in previously published work (6), although not explicitly given, the A: Vm measured using the perforated patch clamp technique for a primary adipocyte in response to equimolar substitution of 138 mM bath Cl Ϫ with I Ϫ .…”

Section: Resultsmentioning

confidence: 82%

Etiology of the membrane potential of rat white fat adipocytes

Bentley

Pulbutr

Chan

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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The plasma membrane potential (Vm) is key to many physiological processes; however, its ionic etiology in white fat adipocytes is poorly characterized. To address this question, we employed the perforated patch current clamp and cell-attached patch clamp methods in isolated primary white fat adipocytes and their cellular model 3T3-L1. The resting Vm of primary and 3T3-L1 adipocytes were Ϫ32.1 Ϯ 1.2 mV (n ϭ 95) and Ϫ28.8 Ϯ 1.2 mV (n ϭ 87), respectively. Vm was independent of cell size and fat content. Elevation of extracellular K ϩ to 50 mM by equimolar substitution of bath Na ϩ did not affect Vm, whereas substitution of bath Na ϩ with the membrane-impermeant cation N-methyl-D-glucamine ϩ -hyperpolarized Vm by 16 mV, data indicative of a nonselective cation permeability. Substitution of 133 mM extracellular Cl Ϫ with gluconate-depolarized Vm by 25 mV, whereas Cl Ϫ substitution with I Ϫ caused a Ϫ9 mV hyperpolarization. Isoprenaline (10 M), but not insulin (100 nM), significantly depolarized Vm. Single-channel ion activity was voltage independent; currents were indicative for Cl Ϫ with an inward slope conductance of 16 Ϯ 1.3 pS (n ϭ 11) and a reversal potential close to the Cl Ϫ equilibrium potential, Ϫ29 Ϯ 1.6 mV. Although the reduction of extracellular Cl Ϫ elevated the intracellular Ca 2ϩ of adipocytes, this was not as large as that produced by elevation of extracellular K ϩ . In conclusion, the Vm of white fat adipocytes is well described by the Goldman-HodgkinKatz equation with a predominant permeability to Cl Ϫ , where its biophysical and single-channel properties suggest a volume-sensitive anion channel identity. Consequently, changes in serum Cl Ϫ homeostasis or the adipocyte's permeability to this anion via drugs will affect its Vm, intracellular Ca 2ϩ , and ultimately its function and its role in metabolic control. adipocyte; white fat; 3T3-L1 cells; chloride; membrane potential THE PLASMA MEMBRANE POTENTIAL (Vm) is a fundamental biological property for the survival and function of virtually every eukarocytic cell. In excitable tissues of animalia, such as the heart, muscles, and nerves, excursions in Vm in the form of action potentials represent the fastest known biological means of intraorganism communication. The action potential often acts to mediate intracellular signaling; for example, an associated influx of extracellular Ca 2ϩ controls functions as diverse as contraction to secretion. In nonexcitable tissues, subtle changes in Vm are involved in the control of the transmembrane and transcellular fluxes of many solutes. Moreover, the membrane potential per se also has an important role to play in basic cell homoeostasis: the regulation of intracellular ionic composition and the maintenance of osmotic equilibrium. A thorough understanding of the etiology of Vm permits us to accurately control it experimentally, a process that allows us to investigate associated physiological and pathological sequelae.

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“…Likewise, there was no evidence for ET B receptors in rat pulmonary artery because sarafotoxin 6c failed to induce vasoconstriction [3]. In enzymatically dispersed VSMC from rat renal artery, the ET B antagonist BQ-788 failed to affect the action of ET-1 in voltage-clamp experiments [29].…”

Section: Discussionmentioning

confidence: 98%

Endothelin A and B receptors of preglomerular vascular smooth muscle cells

Fellner

Arendshorst

2004

Kidney International

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These results indicate that fresh preglomerular VSMC as well as afferent arterioles have both ET(A) and ET(B) receptors, and that the rapid peak [Ca(2+)](i) responses to the ET(B) agonist IRL 1620 are less than half that of subsequent stimulation of ET(A) receptors with ET-1. The similarity of findings in isolated VSMC and afferent arterioles suggests that responses in VSMC in our arteriolar preparation overshadow any potential contribution of endothelial cells when reagents are administered abluminally.

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Electrophysiological effects of endothelin‐1 and their relationship to contraction in rat renal arterial smooth muscle

Cited by 35 publications

References 46 publications

Mechanisms Underlying the Contractile Response to Endothelin-1 in the Rat Renal Artery

Mechanisms Underlying the Contractile Response to Endothelin-1 in the Rat Renal Artery

Etiology of the membrane potential of rat white fat adipocytes

Endothelin A and B receptors of preglomerular vascular smooth muscle cells

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