PMID- 33383853
OWN - NLM
STAT- MEDLINE
DCOM- 20210329
LR  - 20210329
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 1
DP  - 2020 Dec 29
TI  - Cardiac Connexin-43 Hemichannels and Pannexin1 Channels: Provocative 
      Antiarrhythmic Targets.
LID - 10.3390/ijms22010260 [doi]
LID - 260
AB  - Cardiac connexin-43 (Cx43) creates gap junction channels (GJCs) at intercellular 
      contacts and hemi-channels (HCs) at the peri-junctional plasma membrane and 
      sarcolemmal caveolae/rafts compartments. GJCs are fundamental for the direct 
      cardiac cell-to-cell transmission of electrical and molecular signals which 
      ensures synchronous myocardial contraction. The HCs and structurally similar 
      pannexin1 (Panx1) channels are active in stressful conditions. These channels are 
      essential for paracrine and autocrine communication through the release of ions 
      and signaling molecules to the extracellular environment, or for uptake from it. 
      The HCs and Panx1 channel-opening profoundly affects intracellular ionic 
      homeostasis and redox status and facilitates via purinergic signaling 
      pro-inflammatory and pro-fibrotic processes. These conditions promote cardiac 
      arrhythmogenesis due to the impairment of the GJCs and selective ion channel 
      function. Crosstalk between GJCs and HCs/Panx1 channels could be crucial in the 
      development of arrhythmogenic substrates, including fibrosis. Despite the 
      knowledge gap in the regulation of these channels, current evidence indicates 
      that HCs and Panx1 channel activation can enhance the risk of cardiac 
      arrhythmias. It is extremely challenging to target HCs and Panx1 channels by 
      inhibitory agents to hamper development of cardiac rhythm disorders. Progress in 
      this field may contribute to novel therapeutic approaches for patients prone to 
      develop atrial or ventricular fibrillation.
FAU - Andelova, Katarina
AU  - Andelova K
AUID- ORCID: 0000-0002-1499-7687
AD  - Centre of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart 
      Research, 84104 Bratislava, Slovakia.
FAU - Egan Benova, Tamara
AU  - Egan Benova T
AD  - Centre of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart 
      Research, 84104 Bratislava, Slovakia.
FAU - Szeiffova Bacova, Barbara
AU  - Szeiffova Bacova B
AUID- ORCID: 0000-0001-8394-7459
AD  - Centre of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart 
      Research, 84104 Bratislava, Slovakia.
FAU - Sykora, Matus
AU  - Sykora M
AUID- ORCID: 0000-0002-0438-3956
AD  - Centre of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart 
      Research, 84104 Bratislava, Slovakia.
FAU - Prado, Natalia Jorgelina
AU  - Prado NJ
AD  - Instituto de Medicina y Biologia Experimental de Cuyo, Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, M5500 Mendoza, Argentina.
FAU - Diez, Emiliano Raul
AU  - Diez ER
AUID- ORCID: 0000-0001-5163-3703
AD  - Instituto de Medicina y Biologia Experimental de Cuyo, Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, M5500 Mendoza, Argentina.
FAU - Hlivak, Peter
AU  - Hlivak P
AD  - Department of Arrhythmias and Pacing, National Institute of Cardiovascular 
      Diseases, Pod Krasnou Horkou 1, 83348 Bratislava, Slovakia.
FAU - Tribulova, Narcis
AU  - Tribulova N
AUID- ORCID: 0000-0002-5904-4249
AD  - Centre of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart 
      Research, 84104 Bratislava, Slovakia.
LA  - eng
GR  - 2/0002/20, 2/0158/19/Vedecka Grantova Agentura MSVVaS SR a SAV/
GR  - 26230120009/EU ITMS/
GR  - 18-0548, 15-0376/APVV/
PT  - Journal Article
PT  - Review
DEP - 20201229
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Anti-Arrhythmia Agents/pharmacology
MH  - Arrhythmias, Cardiac/etiology/metabolism
MH  - Connexin 43/*metabolism/ultrastructure
MH  - Connexins/*metabolism/ultrastructure
MH  - Disease Susceptibility
MH  - Humans
MH  - *Ion Channel Gating
MH  - Mitochondria, Heart/drug effects/genetics/metabolism/ultrastructure
MH  - Myocardium/*metabolism/ultrastructure
PMC - PMC7795512
OTO - NOTNLM
OT  - Cx43 hemi-channels
OT  - cardiac arrhythmias
OT  - cardio-protection
OT  - mimetic peptides
OT  - pannexin1 channels
COIS- The authors declare no conflict of interest.
EDAT- 2021/01/02 06:00
MHDA- 2021/03/30 06:00
PMCR- 2020/12/29
CRDT- 2021/01/01 01:05
PHST- 2020/11/11 00:00 [received]
PHST- 2020/12/23 00:00 [revised]
PHST- 2020/12/24 00:00 [accepted]
PHST- 2021/01/01 01:05 [entrez]
PHST- 2021/01/02 06:00 [pubmed]
PHST- 2021/03/30 06:00 [medline]
PHST- 2020/12/29 00:00 [pmc-release]
AID - ijms22010260 [pii]
AID - ijms-22-00260 [pii]
AID - 10.3390/ijms22010260 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Dec 29;22(1):260. doi: 10.3390/ijms22010260.