Does the Release of Potassium from Astrocyte Endfeet Regulate Cerebral Blood Flow?

Abstract

Local increases in neuronal activity within the brain lead to dilation of blood vessels and to increased regional cerebral blood flow. Increases in extracellular potassium concentration are known to dilate cerebral arterioles. Recent studies have suggested that the potassium released by active neurons is transported through astrocytic glial cells and released from their endfeet onto blood vessels. The results of computer simulations of potassium dynamics in the brain indicate that the release of potassium from astrocyte endfeet raises perivascular potassium concentration much more rapidly and to higher levels than does diffusion of potassium through extracellular space, particularly when the site of a potassium increase is some distance from the vessel wall. On the basis of this finding, it is proposed that the release of potassium from astrocyte endfeet plays an important role in regulating regional cerebral blood flow in response to changes in neuronal activity.Roy and Sherrington, in 1890, suggested that "the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity" (1, p. 105). Such an intrinsic homeostatic mechanism would help to maintain an adequate supply of oxygen and nutrients to the brain despite widely varying levels of neuronal activity. Although the existence of such a regulatory process has been established (2-5), the mechanism that links neuronal activity and regional cerebral blood flow (rCBF) remains unknown. Interstitial concentrations of potassium and hydrogen ions, adenosine, and several neuro-transmitters vary with neuronal activity. These substances all cause changes in arteriole diameter (6,7) and have been implicated in the regulation of rCBF. However, the relative importance of each of these factors is not known.varies widely during periods of neuronal activity and can rise from a quiescent level of approximately 3 mM to a maximum level of more than 10 mM (8). Cerebral arteries and arterioles (but not capillaries) are extremely sensitive to changes in K + concentration, increasing in diameter as much as 50% in response to a change in [K + ] o from 3 to 10 mM (9,10). This sensitivity to K + could be an important factor in regulating rCBF. Potassium released by active neurons could diffuse through extracellular space to the ablumenal wall of arterioles and cause arteriole dilation. The resulting decrease in vascular resistance (11) would increase rCBF, thus bringing a greater supply of oxygen to precisely the region where it is needed, to the activated portion of the brain. However, arterioles are widely spaced within the brain [they are often separated by more than 500 μim (12)] and may not necessarily be near regions of activated tissue. Thus, the K + released by active neurons would have to diffuse tens or hundreds of micrometers before reaching arterioles and effecting dilation.

Functional Hyperemia and Mechanisms of Neurovascular Coupling in the Retinal Vasculature

“…27 In both mammalian 65 and amphibian 66,67 retinas, A number of years ago, it was proposed that neurovascular coupling is mediated by a feedforward glial cell K þ siphoning mechanism. 68 According to this model, 69 the diffusion of K þ from neurons to blood vessels is enhanced by a K þ current flow through Mü ller cells. The [K þ ] o increase due to neuronal activity generates an influx of K þ into Mü ller cells and results in Mü ller cell depolarization.…”

Astrocytes and Epilepsy

“…K ϩ and water are taken up by the astrocyte membrane facing the neuropil and pushed into the blood and CSF through the end foot membranes under conditions of high neuronal activity. 96 A loss of AQP4 from the perivascular membrane could impair water movements 25 and lead to increased extracellular concentrations of K ϩ , which can depolarize neurons in adjacent regions such as the subiculum. This buffering of K ϩ is probably performed by the GFAP positive subset of GluT-like astrocytes.…”

Model of potassium dynamics in the central nervous system

“…In such a model, the maximum value of r used in the model typically equals 300 pm (the radius of the modeled tissue). In the brain, however, approximately 225 capillaries lie within a cylinder of radius 300 pm (Bar, 1980;Paulson and Newman, 1987). Thus, for all values of r, gglia must be divided by 225 to represent accurately the glial cell conductance associated with a single blood vessel.…”