Multiple Conductance Substates in Pharmacologically Untreated Na+ Channels Generating Persistent Openings in Rat Entorhinal Cortex Neurons |
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Authors: | Jacopo Magistretti Angel Alonso |
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Institution: | (1) Dipartimento di Scienze Fisiologiche-Farmacologiche Cellulari-Molecolari, Università degli Studi di Pavia, Via Forlanini 6, 27100 Pavia, Italy;(2) Department of Neurology and Neurosurgery, McGill University and Montreal Neurological Institute, 3801 University Street, Montréal, H3A 2B4, Québec, Canada |
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Abstract: | Na+-channel activity recorded in cell-attached patches from entorhinal cortex neurons in the absence of gating-modifying drugs
was examined to determine the possible occurrence of substate openings. Brief sojourns to subconductance levels were occasionally
observed within prolonged (“persistent”) burst openings. Subconductance occurrence and amplitude were determined following
two distinct, complementary approaches: (1) direct visual inspection and (2) automated detection by application of a method
that exploits the current variance of fixed-width tracing segments to sort amplitude estimations. The two approaches led to
comparable results. At least six subconductance levels in addition to the full open state were revealed, with amplitudes that
were approximately 20%, 30%, 40%, 50%, 60% and 75% that of full openings. The global probability of subconductance opening
occurrence within a burst as well as the probability of observing one particular subconductance level within a burst showed
no clear dependence upon membrane potential in the −40 to +10 mV range. Open- and closed-time distributions of substate openings could either be similar to those observed in burst full openings
or show distinct patterns. Low-amplitude late openings were also observed in isolation, separately from full-size openings.
These openings corresponded to conductance levels very similar to those of the substates observed within full-size burst openings;
therefore, they were interpreted as isolated subconductance openings. Early, transient openings responsible for the fast-inactivating
whole-cell Na+-current component also manifested distinct conductance levels, the two most prominent of which were in an approximate 75:100
amplitude ratio. Interestingly, the 75% conductance level observed among early openings occurred much more frequently than
in “persistent” burst openings. We conclude that pharmacologically untreated Na+ channels from native neurons generate substate openings that may influence differently the multiple gating modes displayed
by these channels.
Angel Alonso is deceased. |
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Keywords: | Sodium channel Substate Persistent opening Entorhinal cortex Patch clamp Cell-attached |
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