Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic Effect
Connexin 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/11/5/372 |
| _version_ | 1797533424810983424 |
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| author | Felipe Villanelo Jorge Carrasco Joaquin Jensen-Flores Jose Antonio Garate Tomas Perez-Acle |
| author_facet | Felipe Villanelo Jorge Carrasco Joaquin Jensen-Flores Jose Antonio Garate Tomas Perez-Acle |
| author_sort | Felipe Villanelo |
| collection | DOAJ |
| description | Connexin 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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. |
| first_indexed | 2024-03-10T11:14:26Z |
| format | Article |
| id | doaj.art-a6545b9b2e2f470b8283eadb9d536f8a |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-10T11:14:26Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-a6545b9b2e2f470b8283eadb9d536f8a2023-11-21T20:32:15ZengMDPI AGMembranes2077-03752021-05-0111537210.3390/membranes11050372Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic EffectFelipe Villanelo0Jorge Carrasco1Joaquin Jensen-Flores2Jose Antonio Garate3Tomas Perez-Acle4Computational Biology Laboratory, Fundación Ciencia & Vida, Zañartu 1482, Ñuñoa, Santiago 7780132, ChileComputational Biology Laboratory, Fundación Ciencia & Vida, Zañartu 1482, Ñuñoa, Santiago 7780132, ChileComputational Biology Laboratory, Fundación Ciencia & Vida, Zañartu 1482, Ñuñoa, Santiago 7780132, ChileCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2360102, ChileComputational Biology Laboratory, Fundación Ciencia & Vida, Zañartu 1482, Ñuñoa, Santiago 7780132, ChileConnexin 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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.https://www.mdpi.com/2077-0375/11/5/372connexinhemichannelcalcium-bindingsimulation |
| spellingShingle | Felipe Villanelo Jorge Carrasco Joaquin Jensen-Flores Jose Antonio Garate Tomas Perez-Acle Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic Effect Membranes connexin hemichannel calcium-binding simulation |
| title | Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic Effect |
| title_full | Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic Effect |
| title_fullStr | Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic Effect |
| title_full_unstemmed | Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic Effect |
| title_short | Simulations on Simple Models of Connexin Hemichannels Indicate That Ca<sup>2+</sup> Blocking Is Not a Pure Electrostatic Effect |
| title_sort | simulations on simple models of connexin hemichannels indicate that ca sup 2 sup blocking is not a pure electrostatic effect |
| topic | connexin hemichannel calcium-binding simulation |
| url | https://www.mdpi.com/2077-0375/11/5/372 |
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