Ion channel-transporter interactions.
All living cells require membrane proteins that act as conduits for the regulated transport of ions, solutes and other small molecules across the cell membrane. Ion channels provide a pore that permits often rapid, highly selective and tightly regulated movement of ions down their electrochemical gradient. In contrast, active transporters can move moieties up their electrochemical gradient. The secondary active transporters (such as SLC superfamily solute transporters) achieve this by coupling uphill movement of the substrate to downhill movement of another ion, such as sodium. The primary active transporters (including H(+)/K(+)-ATPases and Na(+)/K(+)-ATPases) utilize ATP hydrolysis as an energy source to power uphill transport. It is well known that proteins in each of these classes work in concert with members of the other classes to ensure, for example, ion homeostasis, ion secretion and restoration of ion balance following action potentials. More recently, evidence is emerging of direct physical interaction between true ion channels, and some primary or secondary active transporters. Here, we review the first known members of this new class of macromolecular complexes that we term "chansporters", explore their biological roles and discuss the pathophysiological consequences of their disruption. We compare functional and/or physical interactions between the ubiquitous KCNQ1 potassium channel and various active transporters, and examine other newly discovered chansporter complexes that suggest we may be seeing the tip of the iceberg in a newly emerging signaling modality.
a Bioelectricity Laboratory, Departments of Pharmacology and Physiology and Biophysics, School of Medicine, University of California , Irvine , CA , USA.
Daniel L
DL
Neverisky
a Bioelectricity Laboratory, Departments of Pharmacology and Physiology and Biophysics, School of Medicine, University of California , Irvine , CA , USA.
Geoffrey W
GW
Abbott
D000818:Animals; D001692:Biological Transport; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D016623:Ion Pumps / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D000070590:Solute Carrier Proteins / Q000378:metabolism
D007473:Ion Channels; D016623:Ion Pumps; D026901:Membrane Transport Proteins; D021122:Protein Subunits; D000070590:Solute Carrier Proteins
ATPase; Active transport; KCNQ1; NIS; SMIT1; voltage-gated potassium channel