Abstract: The capillaries of the brain are particularly special, as they are not simply conduits for blood, but are primarily responsible to ensure that the neurons function in a strictly regulated homeostatic interstitium. Brain endothelial cells (BECs) express a plethora of ion channels on its luminal and abluminal surfaces, namely: potassium (K + ) channels (i.e., Kir2 and Kv1), chloride (Cl – )/bicarbonate (HCO3 – ) channels, as well as a number of ion-solute exchangers (Redzic et al., 2011). These channels essentially prioritize vectorial transendothelial transport, especially for the regulation of K + flux across the blood-brain barrier (BBB) (Redzic et al., 2011). The differences between the K + concentration of the brain interstitium and plasma is only 2 mM to 4 mM, but the maintenance of this ionic concentration difference provides a constancy for the neuro- nal resting membrane potential, their associated firing thresholds and the preservation of a constant level of neuronal excitability. The stability of the interstitial environment surrounding the brain’s neurons is the foundational essence of our persona, it is the basis for the continuity of our making of intellectual decisions and the stability of our psycho- logical essence. Furthermore, pathologies emanating from paracellular (PC) tight junction (TJ) permeability have been implicated in psychi- atric disorders, epilepsy, multiple sclerosis, neuroinflammation, stroke and traumatic brain injury (Greene et al., 2019). Thus, the regulation of permeability across the BBB is of interest from a physiological, psycho- logical and clinical perspective.