Villanelo, FelipeCarrasco, JorgeJensen-Flores, JoaquinGarate, Jose AntonioPerez-Acle, Tomas2022-11-302022-11-302021Villanelo, F.; Carrasco, J.; Jensen-Flores, J.; Garate, J.A.; Perez-Acle, T. Simulations on Simple Models of Connexin Hemichannels Indicate That Ca2+ Blocking Is Not a Pure Electrostatic Effect. Membranes 2021, 11, 372. https://doi.org/10.3390/membranes11050372http://repositoriobibliotecas.uv.cl/handle/uvscl/7580Connexin hemichannels allow the unspecific but regulated interchange of molecules from ions to second messenger and ATP, between the eukariotic cell and its extracellular space. The transport of ions and water through hemichannels is important for physiological functions and also in the progression of several pathological conditions. Extracellular Ca2+ concentration is one of the regulators that drives the channel to a closed state. However the relation between their functional and structural states is far for being totally understood. In this work, we modelled connexin hemichannels using simple systems based on a fixed array of carbon atoms and assess the Ca2+ regulation using molecular dynamics simulations. The two proposed mechanism described so far for calcium action were studied combined, e.g., an electrostatic effect and a pore stretching. Our results show that the addition of positive charge density inside the channel cannot stop the flow of potassium, chloride nor water. Only a pore stretching at the center of the pore can explain the channel blocking.Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).HEMICHANNEL; CALCIUM-BINDING; SIMULATIONArticulohttps://doi.org/10.3390/membranes11050372