160
ERNEST SCHOFFENIELS
and shown to result, at least partly, from hormonal variations (102).
In order to explain the enhancement of the active transport of Na, it has
been proposed that curare acts by increasing the passive permeability
to Na of the membrane of the epithelial cells of the skin which face the
outside (100,106).
This results in an increase in potential difference and
in intracellular Na concentration which in turn stimulates the active
transport mechanism for Na.
It is also well demonstrated that the increase in potential difference
is due to an increase in Na permeability, by the fact that, in the presence
of a nonpenetrating anion (S0 4 ) as substitute for CI, no increase in
potential difference is observed, as might be expected from the examination of Eq. 6. The results, however, do not exclude the possibility of a
modification of the CI permeability.
On the basis of studies carried out with 2-PAM and local anesthetics,
it may be concluded that the increase in permeability to Na is brought
about under the following conditions: (a) the compound must be applied to the solution bathing the outside of the skin; (b) the nitrogen
must be cationic; (c) the molecule bearing the cationic nitrogen must
have a particular structure.
If a quaternary nitrogen derivative is made lipid soluble by the addition of a long-chain alkyl group, there is initially an increase in potential difference and active transport of Na, followed by a decrease in
potential difference and an inhibition of active transport (101, 102). The
same effect is observed with local anesthetics if the pH of the outside
solution is such that the compound is mainly in the form of an undissociated base (100). It may thus be concluded from these experiments
that quaternary nitrogen derivatives enhance the passive permeability
to Na of the membrane of the skin facing outside. If they are able to
reach the site of the active transport mechanism, they also inhibit this
mechanism, as shown by our results with 2-PAD (107). As for the local
anesthetics, it is still possible that, since the undissociated base is in
equilibrium with the cationic form at the site of the active transport, the
active transport mechanism may be inhibited by the cationic form.
Lipid-soluble quaternary nitrogen derivatives are ionic detergents.
The effects observed could therefore be due to the fact that the molecules dissolve in some lipid phase of the membrane and thus modify the
structure of the membrane. However, a nonionic detergent, like polyethylene glycol, has no effect on the potential difference or the ion flux
across the frog skin. On the other hand, a cationic detergent (benzalkonium chloride) or an anionic detergent (sodium lauryl sulfate) when
applied on either side of the skin produces first an increase in potential
difference followed by a decrease (109). This is the same type of re-
ERNEST SCHOFFENIELS
and shown to result, at least partly, from hormonal variations (102).
In order to explain the enhancement of the active transport of Na, it has
been proposed that curare acts by increasing the passive permeability
to Na of the membrane of the epithelial cells of the skin which face the
outside (100,106).
This results in an increase in potential difference and
in intracellular Na concentration which in turn stimulates the active
transport mechanism for Na.
It is also well demonstrated that the increase in potential difference
is due to an increase in Na permeability, by the fact that, in the presence
of a nonpenetrating anion (S0 4 ) as substitute for CI, no increase in
potential difference is observed, as might be expected from the examination of Eq. 6. The results, however, do not exclude the possibility of a
modification of the CI permeability.
On the basis of studies carried out with 2-PAM and local anesthetics,
it may be concluded that the increase in permeability to Na is brought
about under the following conditions: (a) the compound must be applied to the solution bathing the outside of the skin; (b) the nitrogen
must be cationic; (c) the molecule bearing the cationic nitrogen must
have a particular structure.
If a quaternary nitrogen derivative is made lipid soluble by the addition of a long-chain alkyl group, there is initially an increase in potential difference and active transport of Na, followed by a decrease in
potential difference and an inhibition of active transport (101, 102). The
same effect is observed with local anesthetics if the pH of the outside
solution is such that the compound is mainly in the form of an undissociated base (100). It may thus be concluded from these experiments
that quaternary nitrogen derivatives enhance the passive permeability
to Na of the membrane of the skin facing outside. If they are able to
reach the site of the active transport mechanism, they also inhibit this
mechanism, as shown by our results with 2-PAD (107). As for the local
anesthetics, it is still possible that, since the undissociated base is in
equilibrium with the cationic form at the site of the active transport, the
active transport mechanism may be inhibited by the cationic form.
Lipid-soluble quaternary nitrogen derivatives are ionic detergents.
The effects observed could therefore be due to the fact that the molecules dissolve in some lipid phase of the membrane and thus modify the
structure of the membrane. However, a nonionic detergent, like polyethylene glycol, has no effect on the potential difference or the ion flux
across the frog skin. On the other hand, a cationic detergent (benzalkonium chloride) or an anionic detergent (sodium lauryl sulfate) when
applied on either side of the skin produces first an increase in potential
difference followed by a decrease (109). This is the same type of re-