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.
"Our knowledge of the Ca 2+ signals in the individual cell types of the intact microcirculation is rudimentary. This is especially the case for pericytes, the cells that have recently been shown to affect diameter in capillaries            and venules    . Pericytes have been described differently depending upon where they have been isolated from, but there has been no systematic study of identified cells in the intact microcirculation, and thus we do not know if contraction and Ca 2+ rises are a universal or a restricted function of pericytes populations [16,20,22,31–36]. "
[Show abstract][Hide abstract] ABSTRACT: The microcirculation is the site of gas and nutrient exchange. Control of central or local signals acting on the myocytes, pericytes and endothelial cells within it, is essential for health. Due to technical problems of accessibility, the mechanisms controlling Ca(2+) signalling and contractility of myocytes and pericytes in different sections of microvascular networks in situ have not been investigated. We aimed to investigate Ca(2+) signalling and functional responses, in a microcirculatory network in situ. Using live confocal imaging of ureteric microvascular networks, we have studied the architecture, morphology, Ca(2+) signalling and contractility of myocytes and pericytes. Ca(2+) signals vary between distributing arcade and downstream transverse and precapillary arterioles, are modified by agonists, with sympathetic agonists being ineffective beyond transverse arterioles. In myocytes and pericytes, Ca(2+) signals arise from Ca(2+) release from the sarcoplasmic reticulum through inositol 1,4,5-trisphosphate-induced Ca(2+) release and not via ryanodine receptors or Ca(2+) entry into the cell. The responses in pericytes are less oscillatory, slower and longer-lasting than those in myocytes. Myocytes and pericytes are electrically coupled, transmitting Ca(2+) signals between arteriolar and venular networks dependent on gap junctions and Ca(2+) entry via L-type Ca(2+) channels. Endothelial Ca(2+) signalling inhibits intracellular Ca(2+) oscillations in myocytes and pericytes via L-arginine/nitric oxide pathway and intercellular propagating Ca(2+) signals via EDHF. Increases of Ca(2+) in pericytes and myocytes constrict all vessels except capillaries. These data reveal the structural and signalling specializations allowing blood flow to be regulated by myocytes and pericytes.
"It seems this signal is communicated in part, but not exclusively, by electrotonic current spread through endothelial gap junctions (Sarelius et al., 2000). Propagated dilation has been observed from cerebral arterioles to arteries (Iadecola et al., 1997) but has not been observed in cerebral capillaries, though propagated constriction has been reported (Peppiatt et al., 2006) and hyperpolarizations have been shown to propagate via gap junctionally coupled pericytes and endothelial cells in isolated retinal capillaries (Wu et al., 2006), suggesting propagated dilation between pericytes is plausible. As seen above, pericyte hyperpolarization is associated with dilation (Puro, 2007) but often only a fraction of pericytes demonstrate a visible alteration in tone, even when they are all electrophysiologically responsive (e.g. "
[Show abstract][Hide abstract] ABSTRACT: Because regional blood flow increases in association with the increased metabolic demand generated by localized increases in neural activity, functional imaging researchers often assume that changes in blood flow are an accurate read-out of changes in underlying neural activity. An understanding of the mechanisms that link changes in neural activity to changes in blood flow is crucial for assessing the validity of this assumption, and for understanding the processes that can go wrong during disease states such as ischaemic stroke. Many studies have investigated the mechanisms of neurovascular regulation in arterioles but other evidence suggests that blood flow regulation can also occur in capillaries, because of the presence of contractile cells, pericytes, on the capillary wall. Here we review the evidence that pericytes can modulate capillary diameter in response to neuronal activity and assess the likely importance of neurovascular regulation at the capillary level for functional imaging experiments. We also discuss evidence suggesting that pericytes are particularly sensitive to damage during pathological insults such as ischaemia, Alzheimer's disease and diabetic retinopathy, and consider the potential impact that pericyte dysfunction might have on the development of therapeutic interventions and on the interpretation of functional imaging data in these disorders.
Frontiers in Neuroenergetics 05/2010; 2(5). DOI:10.3389/fnene.2010.00005
"Notably, in spite of a lack of dye coupling between neighboring pericytes, the constriction observed in response to the electrical stimulation of one cell, was also observed at distant pericyte-controlled regions after a few tens of seconds (Peppiatt et al., 2006). This interesting result suggests that pericytes either release their own diffusible factors which travel appreciable distances to affect adjacent pericytes, or pericytes are communicating to each other by utilizing other cell types, which may include the endothelial cells of the capillary to which pericytes are physically connected via gap junctions (Wu et al., 2006) or the surrounding astrocyte syncytium. The latter possibility may explain why pericytes are sensitive to ATP, which is a ubiquitous astrocyte transmitter utilized for long-range paracrine signaling (Guthrie et al., 1999). "
[Show abstract][Hide abstract] ABSTRACT: The control of cerebral vessel diameter is of fundamental importance in maintaining healthy brain function because it is critical to match cerebral blood flow (CBF) to the metabolic demand of active neurons. Recent studies have shown that astrocytes are critical players in the regulation of cerebral blood vessel diameter and that there are several molecular pathways through which astrocytes can elicit these changes. Increased intracellular Ca(2+) in astrocytes has demonstrated a dichotomy in vasomotor responses by causing the constriction as well as the dilation of neighboring blood vessels. The production of arachidonic acid (AA) in astrocytes by Ca(2+) sensitive phospholipase A(2) (PLA(2)) has been shown to be common to both constriction and dilation mechanisms. Constriction results from the conversion of AA to 20-hydroxyeicosatetraenoic acid (20-HETE) and dilation from the production of prostaglandin E(2) (PGE2) or epoxyeicosatrienoic acid (EET) and the level of nitric oxide (NO) appears to dictate which of these two pathways is recruited. In addition the activation of Ca(2+) activated K(+) channels in astrocyte endfeet and the efflux of K(+) has also been suggested to modify vascular tone by hyperpolarization and relaxation of smooth muscle cells (SMCs). The wide range of putative pathways indicates that more work is needed to clarify the contributions of astrocytes to vascular dynamics under different cellular conditions. Nonetheless it is clear that astrocytes are important albeit complicated regulators of CBF.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.