Endocytosis as a mode to regulate functional expression of two-pore domain potassium (K) channels.

Two-pore domain potassium (K) channels are implicated in an array of physiological and pathophysiological roles. As a result of their biophysical properties, these channels produce a background leak K current which has a direct effect on cellular membrane potential and activity. The regulation of potassium leak from cells through K channels is of critical importance to cell function, development and survival. Controlling the cell surface expression of these channels is one mode to regulate their function and is achieved through a balance between regulated channel delivery to and retrieval from the cell surface. Here, we explore the modes of retrieval of K channels from the plasma membrane and observe that K channels are endocytosed in both a clathrin-mediated and clathrin-independent manner. K channels use a variety of pathways and show altered internalisation and sorting in response to external cues. These pathways working in concert, equip the cell with a range of approaches to maintain steady state levels of channels and to respond rapidly should changes in channel density be required. [ABSTRACT FROM AUTHOR]