Cu2+ Ions Modulate the Conductance Hysteresis of Lysenin Channels

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Lysenin channels self-assembled into lipid membranes have unique biophysical features which distinguish them from other pore-forming toxins. Lysenin channels present hysteretic and asymmetrical voltage-induced gating in response to positive transmembrane voltages and reversible ligand-gating in the presence of multivalent ions. Previous work on lysenin channels reported no apparent dependency between the voltage and ligand gating mechanisms. Such a link is demonstrated by this work, where we show that Cu2+ ions, known to be very potent inhibitors of lysenin channels’ conductance, have a dramatic influence on the channel response to transmembrane voltages. Addition of Cu2+ ions (in the range 0-100 μM) to the solutions bathing a population of lysenin channels inserted into a planar lipid membrane induces the well-known conductance inhibition at any transmembrane voltage within the physiological range. However, the channels that remain open respond to positive voltages by closing. Unexpectedly, only minor changes of the midway voltage of activation and the open probability are encountered, which is indicative of a lack of strong ionic screening induced by Cu2+ ions. In the absence of Cu2+ ions, channel reopening, although it occurs at lower voltages than closing (indicative of hysteresis), is always complete at voltages lower than +10 mV. In the presence of Cu2+ ions, channel reopening is not complete until the voltages reach values as low as −40 mV. This channel arresting in the closed state is concentration dependent and manifests as dramatic changes in the opening and closing rate constants in the presence of Cu2+ ions. The presence of Cu2+ ions significantly accentuate the hysteretic behavior of lysenin channels, indicative of improved molecular memory capabilities. Given the link between hysteresis and memory, our work may open novel avenues for exploiting the voltage-controlled molecular memory for bioelectronics and biological interfacing.