Volume 272, Number 35, Issue of August 29, 1997 pp. 21909-21916
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

The Small Conductance Calcium-activated Potassium Channel Regulates Ion Channel Expression in C3H10T1/2 Cells Ectopically Expressing the Muscle Regulatory Factor MRF4

(Received for publication, May 22, 1997, and in revised form, June 26, 1997)

From the Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907

We investigated small conductance (SK) potassium channel-mediated regulation of muscle-specific, ion channel functional expression in the C3H10T1/2-MRF4 cell model system, a stable fibroblast line ectopically overexpressing the myogenic regulatory transcription factor, MRF4. Mitogenic stimulation of C3H10T1/2-MRF4 cells with basic fibroblast growth factor negatively regulates MRF4 transcriptional activity, inhibiting myogenesis. Using patch clamp techniques we found that mitogenic stimulation of C3H10T1/2-MRF4 cells also up-regulated SK. SK is a charybdotoxin-sensitive, apamin-insensitive channel that exerts positive proliferative control in fibroblasts. Mitogen withdrawal, which removes negative regulation of MRF4 thus initiating myogenesis, also eliminated SK channel currents, coincident both with induction of acetylcholine receptor channels, and up-regulation of muscle inward rectifier potassium channels. Addition of the SK channel blocker charybdotoxin to growth factor-containing culture medium overcame basic fibroblast growth factor-induced negative regulation of MRF4, as evidenced by induction of inward rectifier potassium and acetylcholine receptor channel expression identical to that observed in mitogen-withdrawn cells. Thus, the SK channel can govern electrophysiological phenotype in C3H10T1/2-MRF4 cells, consistent with an ability of SK to affect MRF4-dependent transcriptional activity. SK appears to be a pivotal signaling component for growth factor regulation of both cell proliferation and differentiation.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Pietrangelo, B. Fioretti, R. Mancinelli, L. Catacuzzeno, F. Franciolini, G. Fano, and S. Fulle Extracellular guanosine-5'-triphosphate modulates myogenesis via intermediate Ca2+-activated K+ currents in C2C12 mouse cells J. Physiol., May 1, 2006; 572(3): 721 - 733. [Abstract] [Full Text] [PDF]

				B. Fioretti, T. Pietrangelo, L. Catacuzzeno, and F. Franciolini Intermediate-conductance Ca2+-activated K+ channel is expressed in C2C12 myoblasts and is downregulated during myogenesis Am J Physiol Cell Physiol, July 1, 2005; 289(1): C89 - C96. [Abstract] [Full Text] [PDF]

				T. L. Pena, S. H. Chen, S. F. Konieczny, and S. G. Rane Ras/MEK/ERK Up-regulation of the Fibroblast KCa Channel FIK Is a Common Mechanism for Basic Fibroblast Growth Factor and Transforming Growth Factor-beta Suppression of Myogenesis J. Biol. Chem., April 28, 2000; 275(18): 13677 - 13682. [Abstract] [Full Text] [PDF]