Abstract
BackgroundTransduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF) is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained.Methodology/Principal FindingsWe report on a local control mechanism for regulating inner ear blood flow involving fibrocyte signaling. Fibrocytes in the super-strial region are spatially distributed near pre-capillaries of the spiral ligament of the albino guinea pig cochlear lateral wall, as demonstrably shown in transmission electron microscope and confocal images. Immunohistochemical techniques reveal the inter-connected fibrocytes to be positive for Na+/K+ ATPase β1 and S100. The connected fibrocytes display more Ca2+ signaling than other cells in the cochlear lateral wall as indicated by fluorescence of a Ca2+ sensor, fluo-4. Elevation of Ca2+ in fibrocytes, induced by photolytic uncaging of the divalent ion chelator o-nitrophenyl EGTA, results in propagation of a Ca2+ signal to neighboring vascular cells and vasodilation in capillaries. Of more physiological significance, fibrocyte to vascular cell coupled signaling was found to mediate the sound stimulated increase in cochlear blood flow (CBF). Cyclooxygenase-1 (COX-1) was required for capillary dilation.Conclusions/SignificanceThe findings provide the first evidence that signaling between fibrocytes and vascular cells modulates CBF and is a key mechanism for meeting the cellular metabolic demand of increased sound activity.
Highlights
Sound stimulation applied to the inner ear imposes an energy demand that requires delivery of oxygen and glucose, a demand that requires a well-regulated cochlear blood flow (CBF) to provide both substrate and efficacious clearance of metabolic products
Since fibrocytes participate in ion transport and facilitate generation of the endocochlear potential (EP) by recycling K+ from hair cells to intermediate cells in the stria vascularis through gap junctions [13,18,19], increased hair-cell activity must be matched by increased fibrocyte metabolism
Using confocal and transmission electron microscopy (TEM), we found some fibrocytes in the supra-strial region have interdigitating processes that abut the capillaries (Fig. 1)
Summary
Sound stimulation applied to the inner ear imposes an energy demand that requires delivery of oxygen and glucose, a demand that requires a well-regulated cochlear blood flow (CBF) to provide both substrate and efficacious clearance of metabolic products. While decades of studies from different laboratories have shown that moderate sound activity significantly increases red blood cell velocity, dilates vessels, and decreases local oxygen pressure [1,2,3,4], the underlying physiological mechanisms remain undefined. The model incorporates neural- and autocrine/paracrine-based regulation of vasoconstriction and dilation at the level of the artery and arterioles [5,7]. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF) is a physiological necessity. Despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained
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