PMID- 28232803
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 8
DP  - 2017
TI  - On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 
      Hemichannels Expressed in HeLa Cells.
PG  - 38
LID - 10.3389/fphys.2017.00038 [doi]
LID - 38
AB  - Although connexins (Cxs) are broadly expressed by cells of mammalian organisms, 
      Cx39 has a very restricted pattern of expression and the biophysical properties 
      of Cx39-based channels [hemichannels (HCs) and gap junction channels (GJCs)] 
      remain largely unknown. Here, we used HeLa cells transfected with Cx39 (HeLa-Cx39 
      cells) in which intercellular electrical coupling was not detected, indicating 
      the absence of GJCs. However, functional HCs were found on the surface of cells 
      exposed to conditions known to increase the open probability of other Cx HCs 
      (e.g., extracellular divalent cationic-free solution (DCFS), extracellular 
      alkaline pH, mechanical stimulus and depolarization to positive membrane 
      potentials). Cx39 HCs were blocked by some traditional Cx HC blockers, but not by 
      others or a pannexin1 channel blocker. HeLa-Cx39 cells showed similar resting 
      membrane potentials (RMPs) to those of parental cells, and exposure to DCFS 
      reduced RMPs in Cx39 transfectants, but not in parental cells. Under these 
      conditions, unitary events of ~75 pS were frequent in HeLa-Cx39 cells and absent 
      in parental cells. Real-time cellular uptake experiments of dyes with different 
      physicochemical features, as well as the application of a machine-learning 
      approach revealed that Cx39 HCs are preferentially permeable to molecules 
      characterized by six categories of descriptors, namely: (1) electronegativity, 
      (2) ionization potential, (3) polarizability, (4) size and geometry, (5) 
      topological flexibility and (6) valence. However, Cx39 HCs opened by mechanical 
      stimulation or alkaline pH were impermeable to Ca(2+). Molecular modeling of 
      Cx39-based channels suggest that a constriction present at the intracellular 
      portion of the para helix region co-localizes with an electronegative patch, 
      imposing an energetic and steric barrier, which in the case of GJCs may hinder 
      channel function. Results reported here demonstrate that Cx39 form HCs and add to 
      our understanding of the functional roles of Cx39 HCs under physiological and 
      pathological conditions in cells that express them.
FAU - Vargas, Anibal A
AU  - Vargas AA
AD  - Departamento de Fisiologia, Pontificia Universidad Catolica de Chile Santiago, 
      Chile.
FAU - Cisterna, Bruno A
AU  - Cisterna BA
AD  - Departamento de Fisiologia, Pontificia Universidad Catolica de ChileSantiago, 
      Chile; Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      ValparaisoValparaiso, Chile.
FAU - Saavedra-Leiva, Fujiko
AU  - Saavedra-Leiva F
AD  - Departamento de Fisiologia, Pontificia Universidad Catolica de Chile Santiago, 
      Chile.
FAU - Urrutia, Carolina
AU  - Urrutia C
AD  - Departamento de Fisiologia, Pontificia Universidad Catolica de Chile Santiago, 
      Chile.
FAU - Cea, Luis A
AU  - Cea LA
AD  - Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile 
      Santiago, Chile.
FAU - Vielma, Alex H
AU  - Vielma AH
AD  - Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      Valparaiso Valparaiso, Chile.
FAU - Gutierrez-Maldonado, Sebastian E
AU  - Gutierrez-Maldonado SE
AD  - Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      ValparaisoValparaiso, Chile; Computational Biology Lab (DLab), Fundacion Ciencia 
      & VidaSantiago, Chile.
FAU - Martin, Alberto J M
AU  - Martin AJ
AD  - Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      ValparaisoValparaiso, Chile; Computational Biology Lab (DLab), Fundacion Ciencia 
      & VidaSantiago, Chile.
FAU - Pareja-Barrueto, Claudia
AU  - Pareja-Barrueto C
AD  - Computational Biology Lab (DLab), Fundacion Ciencia & Vida Santiago, Chile.
FAU - Escalona, Yerko
AU  - Escalona Y
AD  - Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      ValparaisoValparaiso, Chile; Computational Biology Lab (DLab), Fundacion Ciencia 
      & VidaSantiago, Chile.
FAU - Schmachtenberg, Oliver
AU  - Schmachtenberg O
AD  - Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      Valparaiso Valparaiso, Chile.
FAU - Lagos, Carlos F
AU  - Lagos CF
AD  - Department of Endocrinology, School of Medicine, Pontificia Universidad Catolica 
      de ChileSantiago, Chile; Facultad de Ciencia, Universidad San SebastianSantiago, 
      Chile.
FAU - Perez-Acle, Tomas
AU  - Perez-Acle T
AD  - Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      ValparaisoValparaiso, Chile; Computational Biology Lab (DLab), Fundacion Ciencia 
      & VidaSantiago, Chile.
FAU - Saez, Juan C
AU  - Saez JC
AD  - Departamento de Fisiologia, Pontificia Universidad Catolica de ChileSantiago, 
      Chile; Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de 
      ValparaisoValparaiso, Chile.
LA  - eng
PT  - Journal Article
DEP - 20170209
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC5298994
OTO - NOTNLM
OT  - Cx39
OT  - dye-uptake
OT  - electrical coupling
OT  - gap junction
OT  - membrane potential
OT  - permeability
OT  - unitary conductance
EDAT- 2017/02/25 06:00
MHDA- 2017/02/25 06:01
PMCR- 2017/02/09
CRDT- 2017/02/25 06:00
PHST- 2016/11/16 00:00 [received]
PHST- 2017/01/13 00:00 [accepted]
PHST- 2017/02/25 06:00 [entrez]
PHST- 2017/02/25 06:00 [pubmed]
PHST- 2017/02/25 06:01 [medline]
PHST- 2017/02/09 00:00 [pmc-release]
AID - 10.3389/fphys.2017.00038 [doi]
PST - epublish
SO  - Front Physiol. 2017 Feb 9;8:38. doi: 10.3389/fphys.2017.00038. eCollection 2017.