Electrical Sorting: The Missing Link between Membrane Potential and Intracellular Vesicle Traffic?

Abstract

The cellular organelle trafhc is dependent on the Na/K gradient and the associated electrical potential across the plasma membrane [1]. However, the l ink between the peripheral membrane potential and the i n tracellular membrane traffic is not known. I n cells, 50—300-nm vesicles connect the different compartments; they carry, for instance, material f r o m the biosynthetic machinery to the plasma membrane and back to the cell interior [1]. I t is well known that the intravesicular organelle trafBc is connected to the Na,K-ATPase {EC 3.6.1.37) activity at the plasma membrane. The Na,K-ATPase, or sodium pump, is regulated essentially by the intracellular Na, M g , and A T P concentrations and by the extracellular K ion concentration. T h e p u m p System also carries an extracellular receptor for cardiac glycosides (for a recent review, see [2]). Occupancy of the receptor by a cardioactive steroid, for example, by the convenient water-soluble d r u g ouabain, immediately blocks the vital coupled Na-extrusion and K-accumulation process that is normally sustained by the plasma membrane Na,K-ATPase, resulting in progressive cellular Na accumulation, K loss, and collapse of the membrane potential. Evidently, the same resuit is obtained by adding ionophores for Na, K, and H ions to cells; because of their high liposolubility, these chemicals rapidly enter the l ipid bilayer, shuttle ions back and f o r t h , and thus destroy the transmembrane ion gradients and potential. Other agents, such as serum, permeabilize plasma membranes by unknown mechanisms.