The Membrane as a Transporter, Ion Channels and Membrane Pumps - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 54

50:1 uphill. For each ATP molecule hydrolyzed, three sodium ions are pumped out
and two potassium ions are pumped in. Ion channels come in three general classes:
(a) voltage-gated, (b) ligand-gated, and (c) so-called gap junctions. They differ not
only in their design geometry, but also in the use of physical and chemical mecha-
nisms for the selection of ions for passage.
In protein-lined channels it is generally accepted that channel-forming peptides
align themselves along the channels. Ions flow through the longitudinal axis of the
channel's interior between cellular exterior and interior regions. Hence, they most
likely experience interactions with channel-forming peptides. Only at the entry and
exit levels of the channels ions are expected to experience interactions with lipids
(similar to the illustration in Fig. 4.1 ). Usually linear, cylindrical, or more complex
types of structures are found in the class of protein-lined channels. This class refers
to highly ordered peptide structures in association with lipids in membranes. Lipids
play an important role in the regulatory phase of the channels, but the creation of
such channels primarily depends on the properties (chemical, electrical, mechanical
including geometry and material, etc.) of both the channel-forming peptides and
lipids in the membrane. The number and type of the amino acid sequences and
other constituents in the peptides, geometrical sizes (length, cross-section, etc.) of
the peptides, and charge properties of the participating atoms and the effective total
charge of the peptides in the hydrophobic membrane environment, etc., all play
crucial roles in the construction of the protein-lined channels. The best examples
of these effects can be found in two special ion channels, namely the gramicidin A
and alamethicin channels. Therefore, this section will be dedicated to discussing key
issues related to protein-lined channels using gramicidin A and alamethicin channels
as important examples.

4.1.1 Gramicidin A Channels

.

3 -helical subunits
or gramicidin A monomers [ 5 , 29 , 52 ]. This channel is formed by reversible, trans-
bilayer association of the subunits [ 37 ]:

6

A gramicidin A channel is a simple dimer of two right-handed, β

k − 1
k 1 M left + M right D

Here, M and D denote a gramicidin A monomer and dimer, respectively. The sub-
scripts (left and right) denote monomers residing in each bilayer leaflet, and k 1
and k

1 are two rate constants determining the channel appearance rate ( f g = −

2 ;

k 1 ·[

1 ).
A schematic representation of the model is shown in Fig. 4.2 . Peptides residing inside
a membrane occasionally approach each other and, depending on the bilayer environ-
ment, associate with each other making a dimer with a very short lifetime, of the order
of milliseconds (ms). The range of channel lifetimes depends on the strength of the

M ] [ M ] being the monomer concentration) and channel lifetime ( τ = 1 / k

−