Potassium Channels and Neurovascular Coupling

Abstract

Neuronal activity is communicated to the cerebral vasculature so that adequate perfusion of brain tissue is maintained at all levels of neuronal metabolism. An increase in neuronal activity is accompanied by vasodilation and an increase in local cerebral blood flow. This process, known as neurovascular coupling (NVC) or functional hyperemia, is essential for cerebral homeostasis and survival. Neuronal activity is encoded in astrocytic Ca 2+ signals that travel to astrocytic processes ('endfeet') encasing parenchymal arterioles within the brain. Astrocytic Ca 2+ signals cause the release of vasoactive substances to cause relaxation, and in some circumstances contraction, of the smooth muscle cells (SMCs) of parenchymal arterioles to modulate local cerebral blood flow. Activation of potassium channels in the SMCs has been proposed to mediate NVC. Here, the current state of knowledge of NVC and potassium channels in parenchymal arterioles is reviewed. (Circ J 2010; 74: 608 - 616)

Inversion of neurovascular coupling by subarachnoid blood depends on large-conductance Ca 2+ -activated K + (BK) channels

“…In brain slices from healthy animals, elevation of endfoot Ca 2+ to <550 nM activates BK channels, increasing perivascular K + to cause vasodilation (19,33). Moderate levels of extracellular K + (<20 mM) cause arteriolar dilation through membrane potential hyperpolarization caused by activation of smooth muscle inward rectifier K + (Kir) channels (19,33,34). Notably, however, levels of extracellular K + greater than ∼20 mM cause arteriolar constriction as the result of a depolarizing shift in the K + equilibrium potential and activation of voltage-dependent Ca 2+ channels.…”

“…The peak increase in Ca 2+ during these spontaneous oscillations was ∼490 nM in brain slices from SAH animals, or ∼170 nM higher than spontaneous events in brain slices of control animals and ∼90 nM greater than EFS-evoked increases in endfoot Ca 2+ in either group. Considering that EFS-induced increases in endfoot Ca 2+ have been shown to increase K + efflux through BK channels (19,21,33), it is reasonable to suppose that these high-amplitude spontaneous events occurring after SAH enhance BK-channel activity to increase basal [K + ] o in the perivascular space between astrocyte endfeet and parenchymal arteriolar myocytes. The narrow gap between astrocyte endfeet and arteriolar smooth muscle membrane prohibits the accurate use of K + -sensing electrodes or dyes to measure [K + ] o directly in this restricted perivascular space.…”

Enhanced Parenchymal Arteriole Tone and Astrocyte Signaling Protect Neurovascular Coupling Mediated Parenchymal Arteriole Vasodilation in the Spontaneously Hypertensive Rat

“…In response to synaptically released glutamate, mGluR activation, putatively in astrocytes, mediates NVC via release of vasodilatory compounds. 1,4 Thus, as an indirect measure of astrocytic contributions to NVC, 14,15 we measured PA luminal diameter changes after mGluR activation with the agonist t-ACPD (100 μmol/L). Figure 6A shows representative traces of t-ACPD-induced dilations.…”

Neurovascular Coupling in Cognitive Impairment Associated With Diabetes Mellitus

“…Recent evidence suggests that astrocytes play a significant role in the regulation of local CBF. 73, 74 Astrocytes grown in high glucose show increased oxidative stress. Prolonged hyperglycemia interferes with astrocytic gap junctional communication.…”