Electrotonic transmission within pericyte-containing retinal microvessels.
ABSTRACT Little is known about the electrotonic architecture of the pericyte-containing retinal microvasculature. Here, the authors focus on the cell-to-cell transmission of hyperpolarization, which can induce abluminal pericytes to relax and lumens to dilate.
With perforated-patch pipettes, the authors monitored the membrane potentials and ionic currents of pairs of pericytes located on freshly isolated rat retinal microvessels. Voltage changes were induced by administering electrical stimuli into pericytes, miniperfusing the KATP channel opener pinacidil, or using oxotremorine to activate chloride channels.
Suggestive of extensive cell-to-cell communication, spontaneous voltage changes were strikingly similar in widely separated pericytes. In addition, injection of current into one of a pair of sampled pericytes always elicited a voltage response in the other sampled pericyte; the gap junction uncoupler, heptanol, blocked this transmission. In the dual recordings, hyperpolarization spreading from a current-injected pericyte decayed approximately 40% within 100 microm. In contrast, pinacidil-induced hyperpolarizations diminished by only approximately 2% in 100 microm. Depolarizations also appeared to spread with similar transmission efficacies.
Based on the experiments, the authors propose that key features of the electrotonic architecture of retinal microvessels include highly efficient cell-to-cell communication within the endothelium and relatively inefficient transmission at pericyte/endothelial junctions. Thus, the endothelium is likely to provide an efficient pathway that functionally links contractile pericytes and thereby, serves to coordinate the vasomotor response of a retinal capillary.
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ABSTRACT: The cerebral hyperaemia is one of the fundamental mechanisms for the central nervous system homeostasis. Due also to this mechanism, oxygen and nutrients are maintained in satisfactory levels, through vasodilation and vasoconstriction. The brain hyperaemia, or coupling, is accomplished by a group of cells, closely related to each other; called neurovascular unit (NVU). The neurovascular unit is composed by neurones, astrocytes, endothelial cells of blood–brain barrier (BBB), myocytes, pericytes and extracellular matrix components. These cells, through their intimate anatomical and chemical relationship, detect the needs of neuronal supply and trigger necessary responses (vasodilation or vasoconstriction) for such demands. Here, we review the concepts of NVU, the coupling mechanisms and research strategies.Acta Physiologica 04/2014; 210(4). DOI:10.1111/apha.12250 · 4.25 Impact Factor
Article: Calcium Signalling in Pericytes[Show abstract] [Hide abstract]
ABSTRACT: Recent advances in pericyte research have contributed to our understanding of the physiology and pathophysiology of microvessels. The microvasculature consists of arteriolar and venular networks located upstream and downstream of the capillaries. Arterioles are surrounded by a monolayer of spindle-shaped myocytes, while terminal branches of precapillary arterioles, capillaries and all sections of postcapillary venules are encircled by a monolayer of morphologically diverse pericytes. There are physiological differences in the response of pericytes and myocytes to vasoactive molecules, suggesting that these two vascular cell types could have different functional roles in the regulation of local blood flow. The contractile activity of pericytes and myocytes is controlled by changes of cytosolic free Ca(2+) concentration. In this short review, we summarize our results and those of other authors on the contractility of pericytes and their Ca(2+) signalling. We describe results regarding sources of Ca(2+) and mechanisms of Ca(2+) release and Ca(2+) entry in control of the spatiotemporal characteristics of the Ca(2+) signals in pericytes. © 2014 S. Karger AG, Basel.Journal of Vascular Research 06/2014; 51(3):190-199. DOI:10.1159/000362687 · 2.44 Impact Factor
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ABSTRACT: PURPOSE: To determine whether an impairment of the autoregulatory mechanism of blood flow in the optic nerve head (ONH) is present in diabetic rabbits and whether the impairment results from the uncoupling of gap junctions. METHODS: Experiments were performed on six alloxan-induced diabetic rabbits and six healthy control animals. In a test of the integrity of the autoregulatory mechanism, the intraocular pressure (IOP) was elevated from the 20-mm Hg baseline to 50 and then to 70 mm Hg. The capillary blood flow in the ONH was measured every 10 minutes by the laser speckle method, with simultaneous measurements of blood pressure. Ocular perfusion pressure (OPP) was calculated at each step, and the relationship between blood flow and OPP was analyzed. In addition, octanol, gap27 (gap junction uncouplers), or balanced saline solution was injected into the vitreous of healthy rabbits, with the balanced saline solution-injected eyes serving as the control. Changes in the ONH blood flow in response to the IOP elevation were determined in the same way. RESULTS: Diabetic rabbits had a significant decrease in ONH blood flow when the OPP was reduced by an elevation of the IOP to 50 or to 70 mm Hg, whereas the ONH blood flow was well maintained in healthy rabbits. After injection of octanol (10.0 mM) or gap27 (10 μM), a reduction of OPP resulted in a significant decrease in ONH blood flow in the healthy rabbits. CONCLUSIONS: These results indicate that autoregulation is disrupted in diabetic animals, and uncoupling the gap junctions in healthy rabbits also disrupts the autoregulation.