Biomedical Engineering Reference
In-Depth Information
monomers forming the conducting dimer starts to become compa-
rable with, and ultimately shorter than, the time required for the
dissociation of the two monomers, such a dissociation becomes
increasingly less probable. The curve calculated on the basis of
this assumption was in good agreement with experiment.
The HERG K
+
channel is present in the plasma membrane
and consists of four identical subunits, each spanning the mem-
brane with six D-helixes. It may exist in one of three confor-
mations: a closed (C), an open (O) and an inactive (I) confor-
mation.
193
At the rest potential, the transmembrane potential
(measured with respect to the potential on the extracellular side of
the plasma membrane, taken conventionally equal to zero) is nega-
tive, and the HERG channel is in the C conformation. If we carry
out a positive potential step that annihilates the transmembrane
potential (a process called depolarization) the channel passes slow-
ly from the C to the O conformation, but very rapidly from the O
to the I conformation; consequently, the resulting outward flux of
potassium ions is small and lasts for about one millisecond. If we
then carry out a subsequent potential step to a value more negative
than the rest potential (a process called hyperpolarization), the
channel passes rapidly from the I to the O conformation and slow-
ly from the O to the C conformation. Consequently, the inward
flux of potassium ions is much higher than the outward flux, and
lasts for more that 100 ms. The HERG K
+
channel was incorpo-
rated in a mercury-supported DPTL/DPhyPC bilayer from its
aqueous solution in the detergent Triton X-100.
184
At a potential of
-300 mV/SCE, corresponding to a transmembrane potential of
+150 mV, the channel is in the I conformation. By stepping the
applied potential to -720 mV/SCE, corresponding to a transmem-
bane potential of about -270 mV, the HERG channel passes rapid-
ly from the I to the O conformation, and then slowly to the C con-
formation.
Figure 16
shows the charge vs. time curve following
this potential step. The charge first increases rapidly due to the
charging of the double layer, and then more slowly, due both to the
flux of potassium ions induced by the opening of the HERG chan-
nel and to the nonspecific ionic flux across the membrane. To ex-
tract the charge ascribed exclusively to the opening of the HERG
channel, the same potential step was repeated after adding WEY, a
specific inhibitor of the HERG channel. By subtracting the charge
transient in the presence of WAY from that in its absence, the
Search WWH ::
Custom Search