Bone as an ion exchange system: Evidence for a pump-leak mechanism devoted to the maintenance of high bone K+

Abstract

To provide evidence of active accumulation of K+ in bone extracellular fluid (BECF), electric currents driven by damaged living metatarsal bones of weanling mice, immersed in physiological media at different [K+], in the presence of blockers of the K+ channels or of the Na+-K+-ATPase inhibitor, were measured by means of a voltage-sensitive two-dimensional vibrating probe. At 4 mM extracellular K+ concentration ([K+](o)), an inward steady current density (7.85-38.53 μA/cm2) was recorded at the damage site, which was significantly dependent on [K+](o). At [K+](o) equal to that of BECF (25 mM), current density was reduced by 76%. At [K+](o) of 0 mM, the current density showed an increase, which was hindered by tetraethylammonium (TEA). Basal current density was reduced significantly after exposure to TEA or BaCl2 and was unchanged after longterm exposure to ouabain. By changing control medium with a chloride-free medium, current density was reversed. The results support the view that K+ excess in bone is maintained by a biologically active cellular system. Because the osteocytebone lining cell syncytium was at the origin of the current in bone, it is likely that this system controls the ionic composition of BECF.