[box type=”download”] An understanding of the functioning of the Na-K ATPase transporter (sodium pump) Appreciation that the sodium pump acts to move ions against concentration gradients The principle of ion channels controlled by electrical or ligand gating [/box]
Routes across membranes:
(i) pores or channels that allow bulk flow of water, ions or sometimes larger molecules, e.g. water channels (aquaporins) and gap junctions connecting the cytosol of adjacent cells;
(ii) transporter molecules move molecules against chemical and/or electrical gradients;
(iii) ion channels, specialized to allow the passage of particular ion species.
A uniporter – can move a single type of molecule in one direction,
A symporter – several different molecules in one direction
An antiporter – different molecules in opposite directions.
Facilitated diffusion – down chemical concentration gradients (energy is provided by concentration gradient). Important transporters for glucose and amino acids, found in the kidney and the gut, are in fact driven by the Na+ electrochemical gradient.
Antiporters such as the Na+–Ca2+ exchanger similarly use the Na+ gradient (One Ca2+ out — for three Na+ into the cell).
These processes are known as secondary active transport, as the Na+ gradient is set up by a process requiring metabolic energy.
The Na+–K+ ATPase, also known as the Na+ pump is an antiporter that uses metabolic energy to move Na+ ions out of the cell and K+ ions in, against their respective concentration gradients.
The ATPase binds extracellular K+ and intracellular Na+ ions and hydrolyses adenosine triphosphate (ATP) to provide the energy needed to change its conformation.
The Na+ pump works continuously, although its activity is stimulated by high intracellular levels of Na+ ions and can be modulated by second messenger-mediated phosphorylation.
The action of the Na+-K+ ATPase is the most important example of primary active transport.
A charged, hydrophilic pore through which ions can move down their electrochemical gradient across the lipid bilayer.
Ion channels are selective for particular ions (only one type of ion or a few related ions).
Channel conductance is the capacity of a channel for an ion.
Ion channel pores are either open or closed; the transition between these states is called gating.
Gating can occur according to the potential difference (voltage gating) across the cell membrane or by the presence of a specific signal molecule (ligand or receptor gating).
Some channels may additionally be modified by phosphorylation of channel proteins by enzymes such as protein kinase C or A.
The voltage-gated fast inward Na+ channel responsible for the upstroke of the action potential has two gates, one that opens as the cell depolarizes beyond ∼–55 mV (its threshold) and another that shuts (inactivates) the channel as the potential becomes positive.
This latter gate can only be reset by repolarization almost to the resting potential.
Some ligand-gated channels are directly gated by extracellular molecules, such as neurotransmitters or hormones, whereas others respond indirectly via intracellular signals, such as diacylglycerol (DAG) or cyclic adenosine monophosphate (cAMP).