DEPOLARIZATION TRANSCRIPTION SIGNALS IN SKELETAL-MUSCLE USE CALCIUM FLUX THROUGH L-CHANNELS, BUT BYPASS THE SARCOPLASMIC-RETICULUM

Membrane depolarization inactivates acetylcholine receptor (AChR) gene s in skeletal muscle. We have studied this process in C2C12 cells, foc using on the role of calcium. Cytoplasmic calcium was monitored with f luo-3, and the activity of receptor genes was measured with a sensitiv e transcript elongation assay. Removal of extracellular calcium or blo ckage of L-type calcium channels disrupts signaling, even when release of calcium from the sarcoplasmic reticulum (SR) is not impeded, where as L channel agonists induce signaling without membrane depolarization or release of calcium from intracellular stores. Activators of calciu m release from the SR do not inhibit AChR genes, either in C2C12 or in chicken skeletal muscle in vivo. It appears that calcium ions do not act as messengers between sarcolemma and nucleus but target a sensor n ear their port of entry where they initiate a signal that bypasses the SR.