C O M M U N I C A T I O N S
and frequent at potentials <10 mV to stable activity at potentials
>10 mV. Using the data at the left (in the Figure), we calculated
the dependence of channel open time as a function of positive
membrane potential that is shown in the right panel of Figure 3.
We note that in this case there is a strong dependence of open time
on transmembrane voltage.
On the basis of the data obtained, we believe that two molecules
of SCMTR associate in the external leaflet of the bilayer. This
assembly creates a pore of approximate diameter 6-7 Å and the
anchor group’s tails penetrate the other bilayer sufficiently for a
transmembrane pore to form. Synthetic modifications and a
structure-activity relationship will be required to confirm this
hypothesis.
The design, preparation, and characterization of the first synthetic
chloride membrane transporter are presented. The novel compound
imparts anion permeability to phospholipid bilayers. The successful
structure, 6, inserts rapidly into liposomes and planar lipid bilayers.
SCMTR has a 1.3 ( 0.01 nS chloride diffusion pathway (>10:1
Cl/K selectivity). SCMTR shows classic channel kinetics and
(open-close) behavior with clear evidence for voltage-dependent
gating. Preliminary data, not presented here, show that SCMTR
also modulates cellular volume in mammalian cells. The high
throughput, ion channel behavior of this simple molecule demon-
strates that even modest synthetic structures can afford selective
membrane permeability equivalent to that seen in protein channels.
Figure 2. Chloride release from liposomes. Liposomes were prepared by
reversed-phase evaporation21 as previously reported.22 Cl- release was
determined with a resin, chloride-specific electrode.23 The kinetics of Cl-
release at 24-154 µM 6 (b) and with 154 µM 7 (O).
Acknowledgment. We warmly thank the National Institutes of
Health (GM 36262), the National Science Foundation (CHE-
9805840), and the Kilo Foundation for grants that supported this
work.
Figure 3. Planar lipid bilayers were formed as previously described.26
SCMTR was applied to the cis chamber at 60 µM with a 450/150 KCl
gradient present across the membrane. Seconds later Cl- currents appeared,
and voltage was varied from +20 to -2 mV. Fractional open time was
computed using Fetchan and pStat, Axon Instruments, CA.
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