Distinct Potassium Channel Types in Brain Capillary Pericytes

Biophys J. 2024 Mar 4:S0006-3495(24)00169-3. doi: 10.1016/j.bpj.2024.03.004. Online ahead of print.ABSTRACTCapillaries, composed of electrically coupled endothelial cells and overlying pericytes, constitute the vast majority of blood vessels in the brain. The most arteriole-proximate three to four branches of the capillary bed are covered by alpha actin-expressing, contractile pericytes. These mural cells have a distinctive morphology and express different markers compared with their smooth muscle cell (SMC) cousins but share similar excitation-coupling contraction machinery. Despite this similarity, pericytes are considerably more depolarized than SMCs at low intravascular pressures. We have recently shown that pericytes, like SMCs, possess functional voltage-dependent Ca2+ channels and ATP-sensitive K+ channels. Here, we further investigate the complement of pericyte ion channels, focusing on members of the K+ channel superfamily. Using NG2-DsRed-transgenic mice and diverse configurations of the patch-clamp technique, we demonstrate that pericytes display robust inward-rectifier K+ currents that are primarily mediated by the Kir2 family, based on their unique biophysical characteristics and sensitivity to micromolar concentrations of Ba2+. Moreover, multiple lines of evidence, including characteristic kinetics, sensitivity to specific blockers, biophysical attributes, and distinctive single-channel properties, established the functional expression of two voltage-dependent K...

Source: Biophysical Journal - March 6, 2024 Category: Physics Authors: Maria Sancho Nicholas R Klug Osama F Harraz David Hill-Eubanks Mark T Nelson Source Type: research