Purinergic G-protein-coupled receptors are ancient and the most abundant group of G-protein-coupled receptors (GPCRs). The wide distribution of purinergic receptors in the cardiovascular system, together with the expression of multiple receptor subtypes in endothelial cells (ECs) and other vascular cells demonstrates the physiological importance of the purinergic signaling system in the regulation of the cardiovascular system. This review discusses the contribution of purinergic P2Y receptors to endothelial dysfunction (ED) in numerous cardiovascular diseases (CVDs). Endothelial dysfunction can be defined as a shift from a “calm” or non-activated state, characterized by low permeability, anti-thrombotic, and anti-inflammatory properties, to a “activated” state, characterized by vasoconstriction and increased permeability, pro-thrombotic, and pro-inflammatory properties. This state of ED is observed in many diseases, including atherosclerosis, diabetes, hypertension, metabolic syndrome, sepsis, and pulmonary hypertension. Herein, we review the recent advances in P2Y receptor physiology and emphasize some of their unique signaling features in pulmonary endothelial cells.

Objective. Methods for the detection of neural signals involve a compromise between invasiveness, spatiotemporal resolution, and the number of neurons or brain regions recorded. Electrode-based probes provide excellent response but usually require transcranial wiring and capture activity from limited neuronal populations. Noninvasive methods such as electroencephalography (EEG) and magnetoencephalography (MEG) offer fast readouts of field potentials or biomagnetic signals, respectively, but have spatial constraints that prohibit recording from single neurons. A cell-sized device that enhances neurogenic magnetic fields can be used as an in situ sensor for magnetic-based modalities and increase the ability to detect diverse signals across multiple brain regions. Approach. We designed a device capable of forming a tight electromagnetic junction with single neurons, thereby transducing changes in cellular potential to magnetic field perturbations by driving current through a nanofabricated inductor element. Main results. We present detailed quantification of the device performance using realistic finite element simulations with signals and geometries acquired from patch-clamped neurons in vitro, and demonstrate the capability of the device to produce magnetic signals readable via existing modalities. We compare the magnetic output of the device to intrinsic neuronal magnetic fields and show that the transduced magnetic field intensity from a single neuron is more than three-fold higher at its peak (1.619 nT vs 0.506 nT). Importantly, we report on a large spatial enhancement of the transduced magnetic field output within a typical voxel (40x40x10 microns) over 250 times higher than the intrinsic neuronal magnetic field strength (0.64 nT vs 2.5 pT). We use this framework to perform optimizations of device performance based on nanofabrication constraints and material choices. Significance. Our quantifications institute a foundation for synthesizing and applying electromagnetic sensors for detecting brain activity and can serve as a general method for quantifying recording devices at the single cell level.