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Molecules. 2017 Nov 25;22(12). pii: E2063. doi: 10.3390/molecules22122063.

Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed in Bacteria.

Author information

1
Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6551, USA. mariana.fiori@ttuhsc.edu.
2
Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6551, USA. srinivas.krishnan21@gmail.com.
3
Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6551, USA. abbey.kjellgren@ttu.edu.
4
Honors College, McClellan Hall, Box 41017, Texas Tech University, Lubbock, TX 79409-1017, USA. abbey.kjellgren@ttu.edu.
5
Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6551, USA. luis.cuello@ttuhsc.edu.
6
Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6551, USA. g.altenberg@ttuhsc.edu.

Abstract

In addition to gap junctional channels that mediate cell-to-cell communication, connexins form hemichannels that are present at the plasma membrane. Since hemichannels are permeable to small hydrophilic compounds, including metabolites and signaling molecules, their abnormal opening can cause or contribute to cell damage in disorders such as cardiac infarct, stroke, deafness, skin diseases, and cataracts. Therefore, hemichannels are potential pharmacological targets. A few aminoglycosides, well-known broad-spectrum antibiotics, have been shown to inhibit hemichannels. Here, we tested several commercially available aminoglycosides for inhibition of human connexin hemichannels using a cell-based bacterial growth complementation assay that we developed recently. We found that kanamycin A, kanamycin B, geneticin, neomycin, and paromomycin are effective inhibitors of hemichannels formed by connexins 26, 43, and 46 (Cx26, Cx43, and Cx46). Because of the >70 years of clinical experience with aminoglycosides and the fact that several of the aminoglycosides tested here have been used in humans, they are promising starting points for the development of effective connexin hemichannel inhibitors.

KEYWORDS:

Cx26; Cx43; Cx46; LB2003; antibiotic; cell-based assay; channel; gap junction; screening; transport

PMID:
29186829
PMCID:
PMC6149774
DOI:
10.3390/molecules22122063
[Indexed for MEDLINE]
Free PMC Article

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