Role of potassium ion diffusion from neurons to capillaries in neurovascular coupling: effects of astrocytic endfeet geometry

Autor: Sara Djurich, Timothy Secomb
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5731717
Popis: Neurovascular coupling (NVC) refers to a local increase in cerebral blood flow (CBF) in response to increased neuronal activity. Diffusion of K+ released by neurons through the extracellular space (ECS) to capillaries may contribute to NVC. Increased perivascular K+ levels can initiate a conducted response that travels to arterioles, triggering vasodilation and increased CBF. Astrocytic endfeet almost completely cover cerebral capillaries, and K+ must diffuse through narrow clefts between endfeet to reach the capillaries. It has therefore been assumed that astrocytes form a barrier to diffusion of K+ in the ECS. The goal of this study is to determine the effects of astrocytic endfeet on the diffusion of K+ from neurons to blood vessels. Two simplified 2D geometries of the ECS, endfeet, and perivascular space (PVS) are used. The first geometry represents diffusion of K+ from a source 1 μm away from a capillary of diameter 5 μm. The second geometry represents K+ diffusion from a neuron 15 μm from the capillary, the average distance between a neuronal soma and the nearest blood vessel. A baseline [K+] of 3 mM is assumed throughout the region. K+ release from neurons is modeled as a prescribed concentration of 12 mM along the outer boundary of the ECS. The time-dependent diffusion equation is used to describe K+ diffusion through the region. Effective diffusivity of K+ is 937.5 μm2/s. Standard conditions are a PVS width of 100 nm and an astrocytic endfeet cleft width of 20 nm, with 2.5 clefts per vessel circumference such that the total width of the clefts represents 0.31% of the capillary’s circumference. In the first geometry, [K+] in the PVS approaches 12 mM within 0.05 s. Decreasing the astrocytic endfeet cleft width to 6.67 nm slows the rise in [K+] to 10 mM at 0.05 s. Increasing PVS width also slows the rise in [K+]. In the second geometry, the rise in [K+] is slower due to the greater diffusion distance and PVS [K+] approaches 12 mM within 0.5 s. Decreasing cleft width or increasing PVS width in the second geometry slightly slows the rise in [K+]. The predicted rise in [K+] at the blood vessel occurs well within the time that increased CBF is observed in NVC, 1-2 seconds. The predicted PVS [K+] levels are sufficient to cause the vasodilation seen in NVC. The present results suggest that direct diffusion of K+ through the ECS is a possible NVC signaling mechanism. Supported by NIH Grant U01 HL133362. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE
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