In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase

Abstract

Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases inneuronal activity. Inconsistent with this hypothesis, intact stimulus-induced vasodilation was observed in inositol 1,4,5-triphosphate(IP3) type-2 receptor (R2) knock-out (KO) mice, in which the primary mechanism of astrocytic calcium increase-the release of calciumfrom intracellular stores following activation of an IP3-dependent pathway-is lacking. Further, our results in wild-type (WT) miceindicate that in vivo onset of astrocytic calcium increase in response to sensory stimulus could be considerably delayed relative to thesimultaneously measured onset of arteriolar dilation. Delayed calcium increases inWTmice were observed in both astrocytic cell bodiesand perivascular endfeet. Thus, astrocytes may not play a role in the initiation of blood flow response, at least not via calcium-dependentmechanisms. Moreover, an increase in astrocytic intracellular calcium was not required for normal vasodilation in the IP3R2-KO animals. © 2013 the authors.