ATP release and hydrolysis contributes to pial arteriolar dilations elicited by neuronal activation

Abstract

Astrocytes may provide a conduit for propagating vasodilating signals from activated neurons to local arterioles, and to upstream arteriolar segments as well. The latter includes pial arterioles in contact with the astrocytic endfeet of the glia limitans (GL). Previous findings from our laboratory, using a highly selective gliotoxin to remove GL influence in vivo, indicated that, irrespective of intensity, neuronal activation-induce pial arteriolar dilation (PAD) was completely dependent upon an intact GL. Previous reports suggested that inter-astrocytic signaling may involve, at least in part, ATP release and purinergic receptor activation. In the present study (using rats equipped with closed cranial windows), we tested the hypothesis that hydrolysis of ATP released from astrocytes (via ectonucleotidase action) plays a key role in neural activation-induced PAD. Thus, we examined the effects of inhibiting adenosine (Ado) receptors or ADP-sensitive P2Y1 receptors (via topical 8-SPT [10 μM] or MRS-2179 [10 μM]) on PADs accompanying excessive neural activation (seizure induced by topically-applied bicuculline) vs physiologic activation (sciatic nerve stimulation [SNS]). Measurements of pial arteriolar diameter increases were made during seizure or SNS, first in the absence and then in the presence of one of the inhibitors. Ado receptor blockade yielded a 60-70% reduction in the PAD elicited by seizure and SNS; whereas P2Y1 blockade was associated with a 33% reduction in the seizure-induced PAD response, but was without effect on the SNS-induced response. These findings indicate that ATP release and breakdown to Ado contributes to the PAD accompanying neuronal activation; although partial hydrolysis products may also play a role during seizure. Supported by the AHA and DK-065629.