Abstract
The currents through single Na+ channels were recorded from dissociated
cells of the flexor digitorum brevis muscle of the mouse. At 15 degrees
C the prolonged bursts of Na+ channel openings produced by application
of the drug DPI 201-106 had brief sojourns to subconductance levels.
The subconductance events were relatively rare and brief, but could
be identified using a new technique that sorts amplitude estimates
based on their variance. The resulting "levels histogram" had a resolution
of the conductance levels during channel activity that was superior
to that of standard amplitude histograms. Cooling the preparation
to 0 degrees C prolonged the subconductance events, and permitted
further quantitative analysis of their amplitudes, as well as clear
observations of single-channel subconductance events from untreated
Na+ channels. In all cases the results were similar: a subconductance
level, with an amplitude of roughly 35\% of the fully open conductance
and similar reversal potential, was present in both drug-treated
and normal Na+ channels. Drug-treated channels spent approximately
3-6\% of their total open time in the subconductance state over a
range of potentials that caused the open probability to vary between
0.1 and 0.9. The summed levels histograms from many channels had
a distinctive form, with broader, asymmetrical open and substate
distributions compared with those of the closed state. Individual
subconductance events to levels other than the most common 35\% were
also observed. I conclude that subconductance events are a normal
subset of the open state of Na+ channels, whether or not they are
drug treated. The subconductance events may represent a conformational
alteration of the channel that occurs when it conducts ions.
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