Ion Transport across Nonexcitable Membranes

Abstract Membrane transport proteins can perform either active or passive ion transport. Active transport, in the absence or against the prevailing electrochemical gradient, can be either primary (ion pumps such as ATPases) or secondary (carriers performing cotransport or exchange). Passive transport of ions, down the electrochemical gradient, is largely mediated by ion channels. In a cell in the steady state, plasma‐membrane active and passive transport processes result in equal and opposite ion fluxes. The ion gradients generate an electrical potential difference (membrane voltage) across the cell membrane because the latter exhibits selective ionic permeability. The resting membrane potential in most cells is largely determined by the K + equilibrium potential, with the cell being negative to the extracellular solution. Ion channels participate in numerous cell functions and their mutations can result in diseases whose manifestations depend on the organs and systems in which these proteins are expressed. Key Concepts: The difference in composition between intracellular and extracellular fluids depends on the barrier and transport functions of the plasma membrane. Transport across the plasma membrane can be by solubility‐diffusion (via the lipid bilayer) or mediated (via membrane proteins). Ion transport is mediated via membrane proteins (channels, carriers or pumps). The differences in ion concentrations across the plasma membrane determine the membrane potential difference (membrane voltage), according to the magnitude of the concentration gradients and the ion permeability. Active transport is thermodynamically uphill (in the absence of or against the electrochemical gradient). It can be primary (pumps), for example, driven by ATP hydrolysis, or secondary (carriers), driven by the electrochemical gradient for one of the substrates. Passive transport can occur by solubility‐diffusion via the lipid bilayer or be mediated by carriers or channels. In the case of ions passive transport is largely via channels. The ion current through channels of one kind depends on the number of channels per cell or unit surface area, their open probability, their conductance and the electrochemical driving force. Ion channels are classified by their selectivity to ions. The most important ion channels expressed on the plasma membrane of nonexcitable cells are selective for K + , Na + , Ca 2+ , H + , Cl − , cations or anions. Numerous genetic diseases of ion channels have been identified. They involve gain‐ or loss‐of‐function mutations that alter the function of one or more organs.