title: Models of neurovascular coupling via potassium and EET signalling.
abstract: Functional hyperemia is an important metabolic autoregulation mechanism by which increased neuronal activity is matched by a rapid and regional increase in blood supply. This mechanism is facilitated by a process known as "neurovascular coupling"--the orchestrated communication system involving neurons, astrocytes and arterioles. Important steps in this process are the production of EETs in the astrocyte and the release of potassium, via two potassium channels (BK and KIR), into the perivascular space. We provide a model which successfully accounts for several observations seen in experiment. The model is capable of simulating the approximate 15% arteriolar dilation caused by a 60-s neuronal activation (modelled as a release of potassium and glutamate into the synaptic cleft). This model also successfully emulates the paradoxical experimental finding that vasoconstriction follows vasodilation when the astrocytic calcium concentration (or perivascular potassium concentration) is increased further. We suggest that the interaction of the changing smooth muscle cell membrane potential and the changing potassium-dependent resting potential of the KIR channel are responsible for this effect. Finally, we demonstrate that a well-controlled mechanism of potassium buffering is potentially important for successful neurovascular coupling.
authors.affiliation: Centre for Bioengineering, University of Canterbury, New Zealand; Van der Veer Institute for Parkinson's and Brain Research, Christchurch, New Zealand.
authors.forename: Hannah
authors.initials: H
authors.lastname: Farr
authors.forename: Tim
authors.initials: T
authors.lastname: David
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001160:Arterioles / Q000502:physiology; D001253:Astrocytes / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008959:Models, Neurological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D015221:Potassium Channels; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D011188:Potassium; D002118:Calcium