By John Ngai/ NIH Director's Blog
Sodium and potassium ions are crucial for governing cell physiology through the regulation of steep concentration gradients across the plasma membrane, ultimately determining membrane potential (Δψ). Notably, over 80% of ion transport processes occur across intracellular membranes, yet it remains uncertain whether ion flux mechanisms within intracellular organelles, such as the Golgi apparatus and lysosomes, operate in a comparable manner.
In two back-to-back Nature Biotechnology papers, Yamuna Krishnan and colleagues report the development of two DNA-based nanodevices, RatiNa and pHlicKer, for imaging intracellular Na+ and K+ at a single-organelle resolution, shedding light on ion dynamics within cellular organelles. They find that endosomes and lysosomes contain high Na+, relative to the cytosol, in both mammalian cells (specifically, mouse macrophages) and Caenorhabditis elegans.
Their study also confirms that the trans-Golgi network (TGN) is a high-K+ compartment and suggests an active role for the Kv11.1 channel in intracellular K+ regulation. These two papers expand the imaging-based molecular toolbox for the study of organelle physiology, offering a complementary approach to organellar patch-clamp methods currently in use.
At the cell’s plasma membrane, large Na+ and K+ gradients are established through the Na+–K+ ATPase. This pump uses roughly one-third of the cell’s total ATP energy consumption to transport three Na+ ions out and two K+ ions into the cell. The resulting flux of Na+ and K+ ions down their steep concentration gradients, facilitated by the plasma membrane Na+ and K+ channels, is responsible for a negative membrane potential (Δψ) of approximately –70 mV at rest. These ion fluxes also drive rapid changes of Δψ, known as action potentials, which involve depolarization followed by repolarization occurring within milliseconds. This phenomenon is characteristic of excitable cells such as neurons and muscle cells during stimulation.