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TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

  • Woo, Jin-Seok (Department of Physiology College of Medicine The Catholic University of Korea) ;
  • Cho, Chung-Hyun (Department of Pharmacology College of Medicine Seoul National University) ;
  • Kim, Do-Han (Department of Life Science Gwangju Institute of Science and Technology) ;
  • Lee, Eun-Hui (Department of Physiology College of Medicine The Catholic University of Korea)
  • Accepted : 2010.07.19
  • Published : 2010.09.30

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 ${\alpha}1_SDHPR$ (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in ${\alpha}1_SDHPR$-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 ${\alpha}1_SDHPR$-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.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

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