Purchase this article with an account.
M. Minami, K. Katsumura, S. Yamanishi, K. Matsushita, D.G. Puro; K+–Induced Vasorelaxation in Pericyte–Containing Retinal Microvessels . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3922.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: K+ released by glial cells ensheathing retinal blood vessels is likely to serve as a vasoactive signal. Recently we observed that unlike vascular smooth muscle, pericytes on retinal microvessels relax when exposed to elevated [K+]o. Our goal was to elucidate the mechanism by which K+ causes pericytes to relax. Methods: Complexes of microvessels were isolated from papain–treated rat retinas; experiments were done within 3h. Changes in pericyte contractility were visualized with the aid of differential interference optics and time–lapse photography. Ionic currents were monitored in pericytes via perforated–patch pipettes. Pericyte calcium was measured using fura–2. Results: Extracellular K+ caused pericytes to relax in a concentration dependent manner; e.g. increasing [K+]o from 3 to 100 mM caused 90% of the responding pericytes to relax. Consistent with this, pericyte calcium decreased in high [K+] solutions even though these cells were significantly depolarized. In contrast, in isolated retinal arterioles, [K+]o elevation caused [Ca2+]i to rise and myocytes to contract. We observed that K+–induced relaxations of pericytes switched to contractions when endothelial/pericyte gap junctions were closed with octanol or GAP 27 or when Na/K pumps were inhibited with ouabain or when Na/Ca exchangers (NCXs) were blocked with KB–R7943 or Ni2+. Under these conditions, pericyte contractions were blocked by the voltage–dependent calcium channel (VDCC) inhibitor, nifedipine. Conclusions: We conclude that the functional relationship between endothelial cells and mural cells is significantly different in retinal capillaries as compared with larger vessels. In capillaries with opened gap junctions, endothelial NCXs, rather than VDCCs, predominate in regulating mural cell Ca2+. As a result, elevated [K+]o induces pericytes to relax by increasing Na/K pump activity which by causing [Na+]i to fall, enhances Ca2+ efflux via endothelial NCXs; this increased NCX activity decreases microvascular Ca2+ and thereby causes pericyte relaxation. However, when gap junctions are closed, pericyte VDCCs potently affect [Ca2+]i, and a K+–induced depolarization causes pericytes to contract.
This PDF is available to Subscribers Only