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<i>Clostridium perfringens</i> type A causes gas gangrene, which involves muscle infection. Both alpha toxin (PLC), encoded by the <i>plc</i> gene, and perfringolysin O (PFO), encoded by the <i>pfoA</i> gene, are important when type A strains cause gas gangrene in a mouse model. This study used the differentiated C2C12 muscle cell line to test the hypothesis that one or both of those toxins contribute to gas gangrene pathogenesis by releasing growth nutrients from muscle cells. RT-qPCR analyses showed that the presence of differentiated C2C12 cells induces <i>C. perfringens</i> type A strain ATCC3624 to upregulate <i>plc</i> and <i>pfoA</i> expression, as well as increase expression of several regulatory genes, including <i>virS/R</i>, <i>agrB/D, </i>and <i>eutV/W</i>. The VirS/R two component regulatory system (TCRS) and its coupled Agr-like quorum sensing system, along with the EutV/W TCRS (which regulates expression of genes involved in ethanolamine [EA] utilization), were shown to mediate the C2C12 cell-induced increase in <i>plc</i> and <i>pfoA</i> expression. EA was demonstrated to increase toxin gene expression. ATCC3624 growth increased in the presence of differentiated C2C12 muscle cells and this effect was shown to involve both PFO and PLC. Those membrane-active toxins were each cytotoxic for differentiated C2C12 cells, suggesting they support ATCC3624 growth by releasing nutrients from differentiated C2C12 cells. These findings support a model where, during gas gangrene, increased production of PFO and PLC in the presence of muscle cells causes more damage to those host cells, which release nutrients like EA that are then used to support <i>C. perfringens</i> growth in muscle.