19 December, 2024: A study led by Mark Nelson, PhD, from the Larner College of Medicine at the University of Vermont, has identified a new mechanism, Electro-Calcium (E-Ca) Coupling, that integrates electrical and calcium signalling to regulate blood flow in the brain. Published in PNAS, the research redefines how capillaries ensure precise oxygen and nutrient delivery to active neurons.
Previously, electrical and calcium signalling were considered independent mechanisms. Nelson’s team discovered that these processes are interconnected. Electrical signals, facilitated by capillary endothelial Kir2.1 channels, spread rapidly across the capillary network, while calcium signals fine-tune local blood flow by triggering vascular responses. E-Ca coupling bridges these systems, with electrical waves enhancing calcium activity, enabling a synchronised response that adjusts blood flow both locally and across larger areas.
Advanced imaging and models showed that electrical signals amplify calcium activity by 76%, improving blood flow regulation. Simulated brain activity further increased calcium signalling by 35%, demonstrating a balanced distribution of blood across the capillary network. This mechanism ensures efficient delivery to areas of greatest demand.
Importantly, the team linked their findings to diseases like Alzheimer’s and small vessel disease, suggesting that restoring E-Ca coupling may correct cerebral blood flow deficits and slow cognitive decline. This research highlights capillaries’ crucial role in brain health and opens avenues for new treatments targeting disrupted blood flow in neurological conditions, including stroke and dementia.
This use-dependent increase in local blood flow (functional hyperemia), mediated by mechanisms collectively termed neurovascular coupling (NVC), is essential for normal brain function and represents the physiological basis for functional magnetic resonance imaging. Furthermore, deficits in cerebral blood flow (CBF) including functional hyperemia are an early feature of small vessel diseases (SVDs) of the brain and Alzheimer’s long before overt clinical symptoms.
Mark Nelson, Ph.D., from the Larner College of Medicine, University of Vermont
