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1Department of Medicine, 2Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; and 3Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts
Submitted 19 October 2007 ; accepted in final form 30 December 2007
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 ([Ca2+]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 [Ca2+]CYT elevation or oscillations, while decreasing adjacent endothelial [Ca2+]CYT. Oscillating currents reversed sign at –30.2 mV and were blocked by niflumic acid, implicating charge transfer via Cl– ion. Removal of extracellular Ca2+, blockade of Ca2+ influx with SKF96365 (30 µmol/l), ryanodine (30 µmol/l), or caffeine (10 mmol/l) inhibited oscillations. In contrast, they were insensitive to removal of extracellular Na+ and exposure to either nifedipine (1 µmol/l) or 2-aminoethoxydiphenyl borate (10 µmol/l). Ouabain (100 nmol/l) increased basal pericyte [Ca2+]CYT and the frequency of resting STICs but did not affect the larger oscillations that followed ANG II stimulation. We conclude that [Ca2+]CYT oscillations stimulate Cl– currents. The former are most likely maintained by repetitive cycles of ryanodine-sensitive SR Ca2+ release and SKF96365-sensitive store refilling.
terminal resistance vessels; blood flow; renal medulla
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