The Membrane as a Transporter, Ion Channels and Membrane Pumps - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 57

Fig. 4.5 Chemotherapy drugs TCC and TXL induced toroidal-type ion pores in a lipid bilayer
membrane, which is possibly associated with a spontaneous change of the pore cross-section. This
new model is explained in recent publications [ 6 , 7 ]
continuously inward, so that the pore is lined by both peptides and lipid head groups.
We have recently observed lipid-lined ion channels being induced by chemotherapy
drugs in model membrane studies [ 6 , 7 ].
4.3 Lipidic Channels in Membranes
In Sects. 4.1 and 4.2 , we have described the structures of a few AMP-induced ion
channels with different structures, which are responsible for an occasional com-
promise of the membrane's insulating properties. Here, we discuss how an ion
channel can be formed by lipids. Although lipids primarily exist across the lipid lay-
ers, in a membrane, ceramides behave differently. Ceramides form channels, called
ceramide channels, due to special organization of ceramides in phospholipid mem-
branes. A ceramide channel is also an example of a lipidic channel. A ceramide is a
lipid molecule, composed of the amino acid sphingosine and a fatty acid. Ceramides
exist in great concentrations in the plasma membrane of a cell, and act as signal-
ing molecules for a number of cellular functions. Ceramides may also play a role
in certain pathological states, including cancer, obesity, diabetes, inflammation, etc.
Understanding ceramide organization in membranes is therefore of great medical
interest. A model structure of ceramide channel is presented in Fig. 4.6 .Fromthe
model diagram, it is clear that the ceramide channels look more like alamethicin's
barrel-stave pore, but have no resemblance to the structures of other channels, like
the toroidal or β -helical types described earlier in this chapter. That means the lipid
membrane adjusts with the complex of ceramide molecules at the channel membrane
interface, and without affecting the membrane thickness, in contrast to what is pro-
posed in the case of toroidal pores. Detailed understanding of the mechanism of the
lipidic channels is still lacking but some insights have been made in the research
papers published by several groups [ 3 , 43 , 48 ].