Overactive ATP-Sensitive K+ Channels Compromise Lymphatic Contractile Function in Cantú Syndrome.

Abstract

he lymphatic system is an extensive network of vessels that uns in parallel to the blood vasculature. Both networks play cruial roles in nourishing and protecting the body. Alongside its ole in “draina ge,” the l ymphatic system is also associated with ultisystem functions and disorders, including metabolic disrders, obesity, neurological disorders, and cardiac growth and e pair. Hence, a better understanding of its structural and funcional physiology and pathophysiology could help in the develpment of future therapeutics for not only traditional lymphatic isorders such as primary and secondary lymphedema but also n the potential treatment of organ-specific functions. Lymphatic vessels, like blood vessels, are composed of a ayer of endothelial cells surrounded by a thin layer of smooth uscle cells. Electrophysiologically, lymphatic smooth muscle LSM) exhibits intrinsic pacemaker properties that allow sponaneous action potential firing, sync hronized contr action w av es, nd facilitation of lymph propulsion against pressure gradients. hile the ion channels r esponsib le for the pacemaker proprties of LSM cells have not been clearly defined, L-type Ca 2 + hannels and ATP-sensiti v e K + (K ATP ) channels are present and rucial for LSM contractility and modulation of spontaneous ontractility, r especti v el y. 1 As well as being present in tissues hroughout the body, K ATP channels are prominently expressed n vascular smooth muscle where they regulate vascular tone nd ther efor e b lood flow. 2–4 Functional K ATP channels ar e a etero-octomeric complex of 4 pore-forming potassium chanel subunits (either Kir6.1 or Kir6.2) and 4 r egulator y sulphonyur ea r ece ptor subunits (either SUR1, SUR2A, or SUR2B). It is now ell esta b lished that the “v ascular smooth m uscle” K ATP chanel is formed of Kir6.1 and SUR2B. 2–4 Evidence from molecular