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Membrane current oscillations in descending vasa recta pericytes.

ABSTRACT: We investigated the origin of spontaneous transient inward current (STIC) oscillations in descending vasa recta (DVR) pericytes. In cells clamped at -80 mV, angiotensin II (ANG II; 10 nmol/l) induced oscillations with mean amplitude and frequency of -65.5 pA and 1.2 Hz. Simultaneous recording of cytoplasmic calcium ([Ca(2+)](CYT)) and membrane current oscillations verified their synchrony and the correlation of their amplitudes. Confocal recording in fluo-4-loaded DVR showed that ANG II can induce either stable pericyte [Ca(2+)](CYT) elevation or oscillations, while decreasing adjacent endothelial [Ca(2+)](CYT). Oscillating currents reversed sign at -30.2 mV and were blocked by niflumic acid, implicating charge transfer via Cl(-) ion. Removal of extracellular Ca(2+), blockade of Ca(2+) influx with SKF96365 (30 micromol/l), ryanodine (30 micromol/l), or caffeine (10 mmol/l) inhibited oscillations. In contrast, they were insensitive to removal of extracellular Na(+) and exposure to either nifedipine (1 micromol/l) or 2-aminoethoxydiphenyl borate (10 micromol/l). Ouabain (100 nmol/l) increased basal pericyte [Ca(2+)](CYT) and the frequency of resting STICs but did not affect the larger oscillations that followed ANG II stimulation. We conclude that [Ca(2+)](CYT) oscillations stimulate Cl(-) currents. The former are most likely maintained by repetitive cycles of ryanodine-sensitive SR Ca(2+) release and SKF96365-sensitive store refilling.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC3196308 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Membrane current oscillations in descending vasa recta pericytes.

Zhang Qingli Q Cao Chunhua C Zhang Zhong Z Wier W Gil WG Edwards Aurélie A Pallone Thomas L TL

American journal of physiology. Renal physiology 20080109 3

We investigated the origin of spontaneous transient inward current (STIC) oscillations in descending vasa recta (DVR) pericytes. In cells clamped at -80 mV, angiotensin II (ANG II; 10 nmol/l) induced oscillations with mean amplitude and frequency of -65.5 pA and 1.2 Hz. Simultaneous recording of cytoplasmic calcium ([Ca(2+)](CYT)) and membrane current oscillations verified their synchrony and the correlation of their amplitudes. Confocal recording in fluo-4-loaded DVR showed that ANG II can indu ...[more]

PMID: 18184740

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Project description:Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important.

Project description:Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism.

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Membrane current oscillations in descending vasa recta pericytes.

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Membrane current oscillations in descending vasa recta pericytes.

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