Received March 7, 2007
Revised April 4, 2007
Accepted after revision April 4, 2007

¹ University of Minnesota

^* To whom correspondence should be addressed. E-mail: ean{at}umn.edu.

	Abstract

Neuronal activity in the central nervous system evokes localized changes in blood flow, a response termed neurovascular coupling or functional hyperemia. Modern functional imaging methods, such as fMRI, measure signals related to functional hyperemia in order to determine localization of brain function and to diagnose disease. The cellular mechanisms that underlie functional hyperemia, however, are not well understood. Glial cells have been hypothesized to be intermediaries between neurons and blood vessels in the control of neurovascular coupling, due to their ability to release vasoactive factors in response to neuronal activity. Using an in vitro preparation of the isolated, intact rodent retina, we have investigated two likely mechanisms of glial control of the vasculature: glial K+ siphoning and glial induction of vasoactive arachidonic acid metabolites. Potassium siphoning is a process by which a K+current flowing through glial cells transfers K+ released from active neurons to blood vessels. Since slight increases in extracellular K+ can cause vasodilation, this mechanism was hypothesized to contribute to neurovascular coupling. Our data, however, suggests that glial K+ siphoning does not contribute significantly to neurovascular coupling in the retina. Instead, we suggest that glial cells mediate neurovascular coupling by inducing the production of two types of arachidonic acid metabolites, EETs and 20-HETE, which dilate and constrict vessels, respectively. We show that both light flashes and direct glial stimulation produce vasodilation or vasoconstriction mediated by EETs and 20-HETE. Further, we show that the type of vasomotor response observed (dilation or constriction) depends on retinal levels of nitric oxide. Our data also demonstrate that glial cells are necessary intermediaries for signaling from neurons to blood vessels, as functional hyperemia does not occur when neuron to glia communication is interrupted. These results indicate that glial cells play an important role in mediating functional hyperemia and suggest that the regulation of blood flow may involve both vasodilating and vasoconstricting components.

Key Words: Arachidonic acid, Glia, Potassium channel

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