MadSci Network: Biochemistry

Re: Tetracaine effect on membrane?

Date: Thu Nov 4 12:01:58 2004
Posted By: Michael Maguire, Professor
Area of science: Biochemistry
ID: 1099489113.Bc

Tetracaine, although charged, has sufficient hydrophobicity to penetrate 
membranes.  Basically, since charged and uncharged forms are always in 
equilibrium, the uncharged form can get through a membrane.  This causes a 
shift in the equilibrium of the remaining tetracaine outside, and more 
uncharged tetracaine forms, which then penetrates the membrane which then 
causes more uncharged tetracaine to form outside and so on and so on.

Second piece of information is that the cytosolic side of all (as far as I 
know) membranes is always negatively charged.  Phosphatidylserine has a 
net charge of -1 and is generally found ONLY on the inner (cytosolic) half 
of the lipid bilayer.  

So, once the tetracaine gets inside, it will equilibrate between its 
charged and uncharged forms again, simply by the Law of Mass Action.  But 
because of the "amphipathic" nature, tetracaine (and other "caines") can 
partially penetrate the membrane with the positive charge interacting with 
the negative charge of the phosphatidylserine.  This causes an "ordering" 
(less fluid)(think partially melted butter) of the head groups of the 
lipids.  However, at the same time, the part of tetracaine in the interior 
of the membrane promotes "disorder" of the fatty acids of each 
phospholipid.  Concentrations of tetracaine and lipids may occur and this 
promotes small "holes" in the membrane and water becomes much more 
permeable across the lipid bilayer.

This mixture of surface "order" and interior "disorder" is what 
(apparently) generates anesthesia.

See the following references.

1:  Yun I, Cho ES, Jang HO, Kim UK, Choi CH, Chung IK, Kim IS, Wood WG. 
 Amphiphilic effects of local anesthetics on rotational mobility in 
neuronal and
model membranes.
Biochim Biophys Acta. 2002 Aug 19;1564(1):123-32. 
PMID: 12101004 [PubMed - indexed for MEDLINE]

2:  Engelke M, Jessel R, Wiechmann A, Diehl HA. 
 Effect of inhalation anaesthetics on the phase behaviour, permeability and
order of phosphatidylcholine bilayers.
Biophys Chem. 1997 Sep 1;67(1-3):127-38. 
PMID: 9397522 [PubMed - indexed for MEDLINE]

3:  Shibata A, Ikawa K, Terada H. 
 Site of action of the local anesthetic tetracaine in a phosphatidylcholine
bilayer with incorporated cardiolipin.
Biophys J. 1995 Aug;69(2):470-7. 
PMID: 8527661 [PubMed - indexed for MEDLINE]

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