Splicing of the muscle-specific plasma membrane Ca(2+)-ATPase isoforms PMCA1c is associated with cell fusion in C2 myocytes.

The regulation of intracellular calcium is essential for proper muscle function. Muscle cells have several mechanisms for dealing with the rapid and large changes in cytosolic calcium level that occur during contraction. Among these is the plasma membrane Ca(2+)-ATPase (PMCA), which pumps calcium from the cytosol to the extracellular space. We have previously shown that in human fetal muscle the PMCA1 isoforms present are PMCA1a-d, with PMCA1b and c predominating. Alternative splicing of mRNAs encoding proteins involved in muscle contraction is common in developing muscle. Therefore, we examined the expression of muscle-specific PMCA mRNAs in pre- and postfusion mouse C2 myoblasts. The housekeeping form of the CA(2+)-ATPase, PMCA1b, was found at all times and under all conditions. However, the other predominating isoform found in muscle, PMCA1c, was expressed on myotube formation. Simple cell-cell contact was not sufficient to induce PMCA1c expression, as cells plated at confluence but harvested before myotubule formation did not express PMCA1c. The induction of this muscle-specific Ca(2+)-ATPase at myotube formation suggests that it may play an important role in muscle function.