Ionic current enhancement through localised membrane geometrical deformation

Abstract

Bleb-inducing aspiration in a patch-clamp has previously been proposed as a controlled proxy for ion channel damage characterisation in brain trauma. Under increasing pressure, voltage gated sodium channels Na${}_{\mathrm{V}}$1.6 have been observed to exhibit an altered dynamics known as “left-shift”. While many numerical models have since been proposed to simulate this behaviour through modification of the ion channel dynamics in the Hodgkin–Huxley model, the effect of the deformed membrane geometry on the electrophysiology has not been explored. Here we reproduce in silico an idealised voltage clamp under the range of pressures used in its in vitro counterparts. The findings show that the geometrical alteration of the membrane within the pipette directly affects the patch electrophysiological measurements without requiring the ion channels to be damaged. This work highlights the need to consider geometrical deformation of the membrane when studying ion channel dynamics in deformed membrane and offers alternative explanations for the effect of blebbing on cellular and brain functions. It also opens the door to the possibility that membrane shape regulation and ionic signal enhancement can act independently with the former influencing the latter in neuronal migration and electrophysiological activity.