title: TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts.
abstract: During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca(2+) channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca(2+)-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca(2+) release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca(2+)-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without alpha1((S))DHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in alpha1((S))DHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or alpha1((S))DHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca(2+) content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Woo
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D056966:Excitation Contraction Coupling; D055785:Gene Knockdown Techniques; D008564:Membrane Potentials; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D000071740:ORAI1 Protein; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002412:Cations; C111842:Mg29 protein, mouse; D009124:Muscle Proteins; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; D019837:Ryanodine Receptor Calcium Release Channel; D016708:Synaptophysin; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C489571:TRPC4 ion channel; D050051:Transient Receptor Potential Channels; D002118:Calcium