Conceptualizing conduction as a pliant electrical response: impact of gap junctions and ion channels.

Abstract

Vasomotor responses conduct among resistance arteries to coordinate blood flow delivery pursuant to energetic demand. Conduction is set by the electrical and mechanical properties of vascular cells, the former tied to how gap junctions and ion channels distribute and dissipate charge, respectively. These membrane proteins are subject to modulation; thus, conduction could be viewed as "pliant" to the current regulatory state. This study used in silico approaches to conceptualize electrical pliancy and to illustrate how gap junctional and ion channel properties distinctly impact conduction along a single skeletal muscle artery or a branching cerebrovascular network. Initial simulations revealed how vascular cells encoded with electrotonic properties best reproduced spreading behavior; the endothelium's importance as a charge source and a longitudinal conduit was readily observed. Alterations in gap junctional conductance produced unique electrical fingerprints: 1) decreased endothelial coupling impaired longitudinal but enhanced radial spread, and 2) reduced myoendothelial coupling limited radial but enhanced longitudinal spread. Subsequent simulations illustrated how tuning ion channel activity, e.g., inward rectifying- and voltage-gated K+ channels, modified charge dissipation, resting membrane potential, and the spread of the electrical phenomenon. Restricting ion channel tuning to a network subregion then revealed how electrical spread could be locally shaped in accordance with the aggregate changes in membrane resistance. In summary, our analysis frames and reimagines electrical conduction as a pliable process, with subtle regulatory changes to membrane proteins shaping network spread and tissue perfusion.NEW & NOTEWORTHY Conducted vasomotor responses depend on initiation and spread of electrical phenomena along arterial walls and their translation into contractile responses. Using computational approaches, we show how subtle but widespread regulation of gap junctions and ion channels can modulate the range and amplitude of electrical spread. Ion channels are regulated by endocrine and mechanical signals and may differ regionally in networks. Subregional electrical changes are not spatially confined but may affect electrical conduction in neighboring regions.