Local Sodium, Global Reach

Abstract

See related article, pages 1030–1038 The plasma membrane (PM) Na+/Ca2+ exchanger (NCX) in vascular smooth muscle is an unique link between the trans-PM Na+ electrochemical gradient and intracellular Ca2+ and, therefore, between Na+ ions and Ca2+ signaling, vascular tone and blood pressure.1 The mechanisms by which Na+ normally enters the myocytes and influences the Na+ gradient and NCX activity are, however, incompletely understood. Our view of how Na+ ions help regulate sarco-/endoplasmic reticulum (S/ER) Ca2+ stores and contractility in arteries has now been signally enhanced by Poburko and colleagues.2 Using CoroNa green, a Na+-sensitive fluorochrome, they observed local Na+ concentration transient increases (“LNats”) in cultured arterial myocytes. The LNats were generated by Na+ entry through cation-selective TRPC6 channels, a member of the TRP (transient receptor potential) channel family.2 This is direct, dynamic evidence for a predicted sub-PM compartment with greatly restricted Na+ diffusion3,4 in which the local rise in Na+ concentration should drive Ca2+ into the myocytes via NCX. The present study has broad implications for Ca2+ homeostasis and signaling. Earlier vascular smooth muscle studies indicated that other members of the TRP channel family might also admit Na+ to sub-PM domains.3,5 Indirect evidence,6 as well as an electron microprobe study, indicate that cardiomyocytes, too, can exhibit elevated local sub-PM Na+ concentrations ([Na+]SPM).7 Moreover, comparable diffusion-restricted, sub-PM cytosolic compartments may also be present in other types of cells (e.g., astrocytes8). To explain how S/ER Ca2+ stores in smooth muscles could refill from the extracellular fluid without inducing contractions,9,10 van Breeman and colleagues postulated a “privileged pathway” (the Ca2+ “buffer …