The degenerin family of proteins in Caenorhabditis elegans is homologous to subunits of the mammalian amiloride-sensitive epithelial sodium channels. Mutations in nematode degenerins cause cell death, probably because of defects in channel function. Genetic evidence was obtained that the unc-105 gene product represents a degenerin homolog affecting C. elegans muscles and that this putative channel interacts with type IV collagen in the extracellular matrix underlying the muscle cell. This interaction may serve as a mechanism of stretch-activated muscle contraction, and this system could provide a molecular model for the activation of mechanosensitive ion channels.