Thursday, June 28, 2007

Ion channels

Ion channels
Ion channels are integral membrane proteins that
allow small specifi c inorganic ions, mainly Na+, K+,
Ca2+ or Cl–, to diffuse rapidly down their electrochemical
gradients across the plasma membrane.
The proteins form a narrow water-fi lled pore across
the membrane through which ions can pass in single
fi le at rates of 106–108 per second – very much faster
rates than transport mediated by carrier proteins. The
pore creates a direct link between the cytosol and the
cell exterior, and therefore there is no need for solute
binding. Ionic diffusion through channels may exhibit
saturation, but usually only when concentrations are
well beyond the physiological range.
Ion channels are highly selective and can distinguish,
among ions of the same charge, those whose
diameters differ by less than 0.1 nm. Selectivity results
from the characteristics of the hydrophilic pore in the
protein, namely its diameter, its shape and the nature
of the electrical charge along its inside surface. Some
ion channels in nerve and muscle membranes are
100 times more permeable to K+ than to Na+, even
though sodium ions are actually smaller than potassium
ions.
Many types of ion channel are responsible for the
electrical excitability of muscle cells, and they mediate
most forms of electrical signalling in the nervous
system. These types are usually closed, opening only
in response to specifi c stimuli and closing rapidly and
spontaneously within milliseconds of having opened.
Such channels are called gated channels, where the
gate is the part of the channel protein that undergoes
conformational change during opening and closing.
One gating episode allows the channel to be in the
transporting mode for as long as it remains open. A
single ion channel operates in an all-or-nothing fashion
– the gate is either open or closed. Gated channels
may open in response to changes in the membrane
potential (voltage-gated channels), to mechanical
stress (mechanically gated channels) or to a ligand
binding to a cell-surface receptor (ligand-gated channels).
The ligand can be either an extracellular mediator
– specifi cally, a neurotransmitter – or an intracellular
mediator, such as an ion or a nucleotide.
Ion pumps
Ion pumps are transmembrane proteins that transport
inorganic ions such as Na+, K+, Ca2+ and H+ in or
out of epithelial cells. The energy that drives the pump
is obtained directly from the hydrolysis of metabolically
derived ATP by an ATPase that is inherent to the
pump. The ATPase attacks the high-energy terminal
phosphate bond of ATP, forming adenosine diphosphate
(ADP). The liberated phosphate is transferred
to a specifi c phosphorylation site in the protein, forming
a high-energy acyl phosphate bond. Hydrolysis of
this bond provides the energy required to elicit a conformational
change in the protein, making the bound
ion accessible to the opposite side of the membrane.
There are three principal classes of ATP-driven ion
pumps, namely P, F and V. Included in the P class are
the Na+–K+-ATPase (sodium pump) and several Ca2+-
ATPases (calcium pumps). All known members of the
F and V classes transport only protons (hydrogen
ions, H+).

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