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1.D.137.  The 5-HT3 (Serotonin) Receptor Nanopore (SR-NP) Family 

The 5-HT3 (serotonin) receptor has been inserted into an artificial membrane an functions has a manipulatable nanopore, responsive to the transmembrane electrical potential (Klesse et al. 2020). These investigators examined the influence of a transmembrane voltage on the hydrophobic gating of nanopores using molecular dynamics simulations. They observed electric field-induced wetting of a hydrophobic gate in a biologically inspired model nanopore based on the 5-HT3 receptor (TC# 1.A.9.2.1)  in its closed state, with a field of at least 100 mV/nm (corresponding to a supra-physiological potential difference of approximately 0.85 V across the membrane) required to hydrate the pore. An unequal distribution of charged residues can generate an electric field intrinsic to the nanopore which, depending on its orientation, can alter the effect of the external field, thus making the wetting response asymmetric. This wetting response could be described by a simple model based on water surface tension, the volumetric energy contribution of the electric field, and the influence of charged amino acids lining the pore. The electric field response was used to determine time constants characterizing the phase transitions of water confined within the nanopore, revealing liquid-vapor oscillations on a time scale of approximately 5 ns. This time scale was largely independent of the water model employed and was similar for different sized pores representative of the open and closed states of the pore. The threshold voltage required for hydrating a hydrophobic gate depends on the orientation of the electric field. These studies provide an attractive perspective for the design of rectifying artificial nanopores (Klesse et al. 2020).

References associated with 1.D.137 family:

Klesse, G., S.J. Tucker, and M.S.P. Sansom. (2020). Electric Field Induced Wetting of a Hydrophobic Gate in a Model Nanopore Based on the 5-HT Receptor Channel. ACS Nano. [Epub: Ahead of Print] 32673478