PBIO SEMINAR SERIES

Coupling of neuronal activity to local cerebral blood flow through astrocytic Ca2+ and BK channels.

Wednesday - October 07, 2009
2009 Lamport Lecture
4:00 pm
T - 639 HSB

Mark T. Nelson, PhD
Professor and Chairman, Pharmacology
 University of Vermont College of Medicine
Speaker's website

Host: Fernando Santana

Functional hyperemia - a vasodilatory response to increased neuronal activity - ensures an adequate supply of nutrients and oxygen to active brain regions. Increased intracerebral blood flow in response to neuronal activity is a fundamental physiological process that is exploited diagnostically, forming the basis for techniques such as functional magnetic resonance imaging (fMRI), which uses both perfusion and blood oxygenation level-dependent (BOLD) contrast to map brain function. Recent evidence indicates that neuronal activity is encoded in astrocytes in the form of dynamic intracellular Ca2+ signals, which travel to astrocytic processes ("endfeet") encasing the arterioles in the brain. Astrocytic Ca2+ signaling has been implicated in the dilatory response of adjacent arterioles, in keeping with the functional linkage between neuronal activity and enhanced local blood flow. Paradoxically, however, astrocytic Ca2+ signals have also been linked to constriction. Here we show that regardless of the mechanism by which astrocytic endfoot Ca2+ was elevated, modest increases in Ca2+ induced dilation, while larger increases switched dilation to constriction. Large-conductance, Ca2+-sensitive potassium (BK) channels in astrocytic endfeet mediated a majority of the dilation and the entire vasoconstriction, implicating local extracellular K+ as a vasoactive signal for both dilation and constriction. These results provide evidence for a unifying mechanism that explains the nature and apparent duality of the vascular response, showing that the degree and polarity of neurovascular coupling depends on astrocytic endfoot Ca2+, BK channels and perivascular K+. Furthermore, evidence will be provided that subarachnoid hemorrhage switches the polarity of neurovascular coupling, such that "normal" elevations of astrocytic endfoot Ca2+ cause arteriolar constriction, not dilation.