Conceptualizing Conduction as a Pliant Vasomotor response: Impact of Ca fluxes and Ca Sensitization.

Coordinating blood flow to active tissue requires vasomotor responses to conduct among resistance arteries. Vasomotor spread is governed by the electrical and mechanical properties of vessels; the latter being linked to the sigmoid relations between membrane potential (V), [Ca], and smooth muscle contractility. Proteins guiding electrical-to-tone translation are subject to regulation; thus, vasomotor conduction could be viewed as "pliant" to the current regulatory state. Using simple in silico approaches, we explored vasomotor pliancy and how the regulation of contractility impacts conduction along a skeletal muscle artery and a branching cerebrovascular network. Initial simulations revealed how limited electromechanical linearity affects the translation of electrical spread into arterial tone. Subtle changes to the V-[Ca] or [Ca]-diameter relationship, akin to regulatory alterations in Ca influx and Ca sensitivity, modified the distance and amplitude of the conducted vasomotor response. Simultaneous changes to both relationships, consistent with agonist stimulation, augmented conduction although the effect varied with stimulus strength and polarity (depolarization vs hyperpolarization). Final simulations using our cerebrovascular network revealed how localized changes to the V-[Ca] or [Ca]-diameter relationships could regionally shape conduction without interfering with the electrical spread. We conclude that regulatory changes to key effector proteins (e.g. L-type Ca channels, myosin light chain phosphatase), integral to voltage translation, not only impact conducted vasomotor tone but likely blood flow delivery to active tissues.