Electrophysiological engineering of heart-derived cells with calcium-dependent potassium channels improves cell therapy efficacy for cardioprotection.
Animals
Calcium
/ metabolism
Cell Proliferation
/ drug effects
Cell- and Tissue-Based Therapy
/ methods
Cytokines
Electrophysiological Phenomena
/ drug effects
Gene Expression Regulation
Heart
Humans
Intermediate-Conductance Calcium-Activated Potassium Channels
/ genetics
Ischemia
Membrane Potentials
/ physiology
Mice
Myocardium
/ metabolism
Nanoparticles
Potassium
/ metabolism
Potassium Channel Blockers
/ pharmacology
Potassium Channels, Calcium-Activated
/ genetics
Stem Cells
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 08 2021
16 08 2021
Historique:
received:
03
07
2019
accepted:
21
07
2021
entrez:
17
8
2021
pubmed:
18
8
2021
medline:
31
8
2021
Statut:
epublish
Résumé
We have shown that calcium-activated potassium (KCa)-channels regulate fundamental progenitor-cell functions, including proliferation, but their contribution to cell-therapy effectiveness is unknown. Here, we test the participation of KCa-channels in human heart explant-derived cell (EDC) physiology and therapeutic potential. TRAM34-sensitive KCa3.1-channels, encoded by the KCNN4 gene, are exclusively expressed in therapeutically bioactive EDC subfractions and maintain a strongly polarized resting potential; whereas therapeutically inert EDCs lack KCa3.1 channels and exhibit depolarized resting potentials. Somatic gene transfer of KCNN4 results in membrane hyperpolarization and increases intracellular [Ca
Identifiants
pubmed: 34400625
doi: 10.1038/s41467-021-25180-8
pii: 10.1038/s41467-021-25180-8
pmc: PMC8368210
doi:
Substances chimiques
Cytokines
0
Intermediate-Conductance Calcium-Activated Potassium Channels
0
KCNN4 protein, human
0
Kcnn4 protein, mouse
0
Potassium Channel Blockers
0
Potassium Channels, Calcium-Activated
0
Potassium
RWP5GA015D
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4963Subventions
Organisme : CIHR
ID : 148401
Pays : Canada
Organisme : CIHR
ID : 162088
Pays : Canada
Informations de copyright
© 2021. The Author(s).
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