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Hajime Kawamura, Hidehiro Oku, Qing Li, Kenji Sakagami, Donald G. Puro; Endothelin-Induced Changes in the Physiology of Retinal Pericytes. Invest. Ophthalmol. Vis. Sci. 2002;43(3):882-888.
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purpose. Pericytes are positioned on the abluminal wall of capillaries
and are thought to play a role in regulating retinal blood flow.
Although endothelin (ET)-1 is a putative endothelium–pericyte signal,
the mechanisms by which this molecule regulates pericyte function
remain unclear. Because ion channels play a vital role in the response
of pericytes to extracellular signals, this study was undertaken to
assess the effects of ET-1 on ionic currents.
methods. The perforated-patch configuration of the patch-clamp technique was
used to monitor whole-cell currents of pericytes located on
microvessels freshly isolated from the rat retina. To assay
cell-to-cell coupling within retinal microvessels, a gap
junction–permeant tracer was loaded through patch pipettes
into pericytes and the spreading of the tracer detected by
results. ET-1 acting through ETA receptors altered pericyte currents
and caused depolarization of the membrane potential. The effects on
pericyte currents were dynamic over time. Initially, the nonspecific
cation (NSC) and calcium-activated chloride (ClCa) currents
were activated and the adenosine triphosphate (ATP)–sensitive
potassium (KATP) current inhibited. Subsequently, by a
mechanism sensitive to a protein kinase C (PKC) inhibitor, the NSC,
ClCa, and voltage-dependent potassium currents diminished
as gap junction pathways closed within the microvessels.
conclusions. ET-1 regulates pericyte conductances by multiple mechanisms. One
process involves a PKC-dependent closure of gap junction pathways
resulting in loss of electrotonic input from neighboring cells. Thus,
ET-1 not only affects individual microvascular cells, but also
regulates the effective size of the multicellular functional units that
may serve to control capillary blood flow. This regulation of
intercellular communication within pericyte-containing microvessels may
be an important, previously unrecognized, action of
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