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Biophys J, January 2002, p. 193-205, Vol. 82, No. 1



and
*Department of Biology, University of Maryland, College Park,
Maryland 20742,
Laboratory of Physical and Structural
Biology, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland 20892 USA,
and
St. Petersburg Nuclear Physics Institute,
Gatchina 188350, Russia
Nucleotide penetration into the voltage-dependent
mitochondrial ion channel (VDAC) reduces single-channel conductance and generates excess current noise through a fully open channel. VDAC channels were reconstituted into planar phospholipid membranes bathed
in 1.0 M NaCl. At a given nucleotide concentration, the average
decrease in small-ion channel conductance induced by mononucleotides ATP, ADP, AMP, and UTP and dinucleotides
- and
-NADH, NAD, and NADPH are very close. However, the excess current noise is about seven
times higher in the presence of NADPH than in the presence of ATP and
is about 40 times higher than in the presence of UTP. The
nucleotide-generated low-frequency noise obeys the following sequence:
-NADPH >
-NADH =
-NADH > ATP > ADP >
-NAD
AMP > UTP. Measurements of bulk-phase
diffusion coefficients and of the effective charge of the nucleotides
in 1.0 M NaCl suggest that differences in size and charge cannot be the
major factors responsible for the ability to generate current noise.
Thus, although the ability of nucleotides to partition into the
channel's pore, as assessed by the reduction in conductance, is very
similar, the ability to generate current noise involves a detailed
recognition of the three-dimensional structure of the nucleotide by the
VDAC channel. A possible mechanism for this selectivity is two
noise-generating processes operating in parallel.
Biophys J, January 2002, p. 193-205, Vol. 82, No. 1
© 2002 by the Biophysical Society 0006-3495/02/01/193/13 $2.00
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