Cell cycle-dependent expression of Kv1.5 is involved in myoblast proliferation
Núria Villalonga1, Ramón Martínez-Mármol, Meritxell Roura-Ferrer
1Molecular Physiology Laboratory, Departament de Bioquímica i Biología Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain.
Abstract:
Voltage-dependent K(+) channels (Kv) are involved in the proliferation of many types of cells, but the mechanisms by which their activity is related to cell growth remain unclear. Kv antagonists inhibit the proliferation of mammalian cells, which is of physiological relevance in skeletal muscle. Although myofibres are terminally differentiated, some resident myoblasts may re-enter the cell cycle and proliferate. Here we report that the expression of Kv1.5 is cell-cycle dependent during myoblast proliferation. In addition to Kv1.5 other Kv, such as Kv1.3, are also up-regulated. However, pharmacological evidence mainly implicates Kv1.5 in myoblast growth. Thus, the presence of S0100176, a Kv antagonist, but not margatoxin and dendrotoxin, led to cell cycle arrest during the G(1)-phase. The use of selective cell cycle blockers showed that Kv1.5 was transiently accumulated during the early G(1)-phase. Furthermore, while myoblasts treated with S0100176 expressed low levels of cyclin A and D(1), the expression of p21(cip-1) and p27(kip1), two cyclin-dependent kinase inhibitors, increased. Our results indicate that the cell cycle-dependent expression of Kv1.5 is involved in skeletal muscle cell proliferation.
Insights
Voltage-dependent potassium channels (Kv) are crucial for skeletal muscle cell proliferation. Kv1.5 expression is cell-cycle dependent, with antagonists halting myoblast growth by arresting the cell cycle.
Area of Science:
- Molecular Biology
- Cell Biology
- Physiology
Background:
- Voltage-dependent potassium channels (Kv) play a role in cell proliferation, but their precise mechanisms in cell growth are not fully understood.
- Kv channel antagonists inhibit mammalian cell proliferation, a finding with physiological relevance in skeletal muscle.
- Skeletal muscle myofibers are terminally differentiated, yet resident myoblasts can re-enter the cell cycle and proliferate.
Purpose of the Study:
- To investigate the role of Kv channels, specifically Kv1.5, in skeletal muscle cell proliferation.
- To determine the cell-cycle dependency of Kv channel expression during myoblast proliferation.
- To elucidate the molecular mechanisms by which Kv channel activity influences myoblast cell cycle progression.
Main Methods:
- Analysis of Kv channel expression during myoblast proliferation.
- Pharmacological inhibition of Kv channels using selective antagonists (S0100176, margatoxin, dendrotoxin).
- Cell cycle analysis using flow cytometry and assessment of cell cycle regulatory proteins (cyclins, cyclin-dependent kinase inhibitors).
Main Results:
- Kv1.5 expression was found to be cell-cycle dependent during myoblast proliferation, with transient accumulation during early G1-phase.
- The Kv antagonist S0100176, but not margatoxin or dendrotoxin, induced cell cycle arrest at the G1-phase.
- S0100176 treatment led to decreased expression of cyclin A and D1, and increased expression of p21(cip-1) and p27(kip1).
Conclusions:
- Cell cycle-dependent expression of Kv1.5 is implicated in the proliferation of skeletal muscle cells.
- Kv1.5 activity appears to be a key regulator of myoblast progression through the G1-phase of the cell cycle.
- These findings highlight Kv1.5 as a potential therapeutic target for modulating skeletal muscle regeneration and growth.
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