The role of astrocytic calcium and TRPV4 channels in neurovascular coupling

AbstractNeuronal activity evokes a localised change in cerebral blood flow in a response known as neurovascular coupling (NVC). Although NVC has been widely studied the exact mechanisms that mediate this response remain unclear; in particular the role of astrocytic calcium is controversial. Mathematical modelling can be a useful tool for investigating the contribution of various signalling pathways towards NVC and for analysing the underlying cellular mechanisms. The lumped parameter model of a neurovascular unit with both potassium and nitric oxide (NO) signalling pathways and comprised of neurons, astrocytes, and vascular cells has been extended to include the glutamate induced astrocytic calcium pathway with epoxyeicosatrienoic acid (EET) signalling and the stretch dependent TRPV4 calcium channel on the astrocytic endfoot. Results show that the potassium pathway governs the fast onset of vasodilation while the NO pathway has a delayed response, maintaining dilation longer following neuronal stimulation. Increases in astrocytic calcium concentration via the calcium signalling pathway and/or TRPV4 channel to levels consistent with experimental data are insufficient for inducing either vasodilation or constriction, in contrast to a number of experimental results. It is shown that the astrocyte must depolarise in order to produce a significant potassium flux through the astrocytic BK channel. However astrocytic calcium is shown to strengthen potassium induced NVC by opening th...
Source: Journal of Computational Neuroscience - Category: Neuroscience Source Type: research