Prostaglandin E2, a postulated astrocyte-derived neurovascular coupling agent, constricts rather than dilates parenchymal arterioles.

It has been proposed that prostaglandin E(2) (PGE(2)) is released from astrocytic endfeet to dilate parenchymal arterioles through activation of prostanoid (EP(4)) receptors during neurovascular coupling. However, the direct effects of PGE(2) on isolated parenchymal arterioles have not been tested. Here, we examined the effects of PGE(2) on the diameter of isolated pressurized parenchymal arterioles from rat and mouse brain.

Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow.

Calcium-sensitive potassium (K(Ca)) channels have been shown to modulate the diameter of cerebral pial arteries; however, little is known regarding their roles in controlling cerebral parenchymal arterioles (PAs). We explored the function and cellular distribution of small-conductance (SK(Ca)) and intermediate-conductance (IK(Ca)) K(Ca) channels and large-conductance K(Ca) (BK(Ca)) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK(Ca) and IK(Ca) channels conducted the outward current in isolated PA ECs (current densities, ~20 pA/pF and ~28 pA/pF at +40 mV, respectively), but these currents were not detected in PA SMCs.

Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and constriction.

Neuronal activity is thought to communicate to arterioles in the brain through astrocytic calcium (Ca(2+)) signaling to cause local vasodilation. Paradoxically, this communication may cause vasoconstriction in some cases. Here, we show that, regardless of the mechanism by which astrocytic endfoot Ca(2+) was elevated, modest increases in Ca(2+) induced dilation, whereas larger increases switched dilation to constriction.

Regulation of intracerebral arteriolar tone by K(v) channels: effects of glucose and PKC.

Voltage-gated potassium (K(v)) channels in vascular smooth muscle cells (VSMC) are critical regulators of membrane potential and vascular tone. These channels exert a hyperpolarizing influence to counteract the depolarizing effects of intraluminal pressure and vasoconstrictors. However, the contribution of K(v) channel activity to the functional regulation of cerebral (parenchymal) arterioles within the brain is not known.

Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections.

Calcium (Ca(2+)) release through inositol 1,4,5-trisphosphate receptors (IP(3)Rs) regulates the function of virtually every mammalian cell. Unlike ryanodine receptors, which generate local Ca(2+) events ("sparks") that transmit signals to the juxtaposed cell membrane, a similar functional architecture has not been reported for IP(3)Rs. Here, we have identified spatially fixed, local Ca(2+) release events ("pulsars") in vascular endothelial membrane domains that project through the internal elastic lamina to adjacent smooth muscle membranes.