Computational Investigation of the Mechanism Behind Sidearm-Mediated Neurofilament Interaction

Abstract

estimated to contain 2.9x10 7 tetramers. The channel conductance was undetectable with symmetrical pH 7.5 at À30 mV (trans relative to cis). Upon acidification of the cis chamber to pH 5.5 (and stirring), there was a smooth increase in current to a level of 633 pS (À19 pA, i.e. current flow from cis to trans, 4.1 protons/tetramer/s). Then, amantadine was injected cis and trans to a concentration of 0.1 mM. Stirring cis produced 79% block over the course of 5.6 minutes. The residual current was constant for the next 5.6 min. Then, cis neutralization eliminated the residual current. Rechallenge with cis acidification (with amantadine present) showed persistence of block. Acidification and amantadine sensitivity of this construct matches with those observed for other Influenza A M2 constructs in Xenopus oocytes and MEL cells. Similar results were observed in two additional folded-bilayer experiments and further studies are in progress.