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Control of human myoblast differentiation by membrane potential and ionic channel activity

English title Control of human myoblast differentiation by membrane potential and ionic channel activity
Applicant Bernheim Laurent
Number 105331
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Physiology : other topics
Start/End 01.10.2004 - 31.03.2009
Approved amount 439'833.00
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All Disciplines (2)

Discipline
Physiology : other topics
Embryology, Developmental Biology

Keywords (7)

Human muscle; myoblast differentiation; ionic channels; membrane potential; electrophysiology; myogenic transcription factors; calcium indicators

Lay Summary (English)

Lead
Lay summary
The general goal of our lab is to study human skeletal muscle regeneration. Muscle regeneration is a paradigm of a differentiation process as it involves myogenic differentiation factors, it is controlled by extracellular growth factors and mediators, and it works through the activation of multiple intracellular signaling pathways. Our starting material is the satellite cell, the myogenic stem cell of skeletal muscle. Upon muscle injury, satellite cells proliferate as myoblasts and, after a process of differentiation, fuse together to generate new muscle fibers. Our objective is to understand the interplay between ionic channels, resting membrane potential, intracellular calcium, and various enzymes or myogenic regulatory factors activated during the differentiation process of myoblasts. We discovered that a membrane hyperpolarization is not only among the earliest steps in myoblast differentiation but is also required for the differentiation process to take place. This membrane hyperpolarization results from an up regulation of two potassium channels: ether à-go-go and Kir2.1 inward rectifying potassium channels. We found that the purpose of the differentiation-linked hyperpolarization is to generate calcium influxes mainly via store-operated Orai1 channels and voltage-gated T-type calcium channels. These calcium influxes, in turn, via the CaMK and calcineurin pathways, activate the myogenic transcription factors myogenin and MEF2, two transcription factors crucial for myoblast differentiation.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Name Institute

Associated projects

Number Title Start Funding scheme
124910 Postnatal human myogenesis is controlled by ionic channel activity and two sequential Ca2+-signals that activate specific signaling pathways 01.04.2009 Project funding (Div. I-III)
65409 Ionic channels, calcium signals, and differentiation factors during human myoblast fusion 01.10.2001 Project funding (Div. I-III)

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