| Summary: | Posterior body wall muscle contraction (pBoc) in C. elegans occurs rhythmically and mediates defecation. pBoc is controlled by IP 3 ‐dependent Ca 2+ oscillations in the intestine. The intestinal epithelium can be studied by patch clamp electrophysiology, Ca 2+ imaging, reverse/forward genetics analysis, molecular biology and thus provides a powerful model to develop an integrated understanding of a non‐excitable cell oscillatory Ca 2+ signaling pathway. Intestinal cells express a TRPM‐like outwardly rectifying Ca 2+ (ORCa) current. Two TRPM homologs, GON‐2 and GTL‐1, are expressed in the intestine. Using deletion and severe loss‐of‐function alleles of the gtl‐1 and gon‐2 genes, we demonstrate that GON‐2 and GTL‐1 are both required for maintaining rhythmic pBoc and intestinal Ca 2+ oscillations. Loss of GTL‐1 and GON‐2 function inhibits I ORCa ∼70% and ∼90%, respectively. I ORCa is undetectable in gon‐2; gtl‐1 double mutant cells. Our results demonstrate that 1) both gon‐2 and gtl‐1 are required for ORCa channel function, and 2) GON‐2 and GTL‐1 function interdependently to mediate I ORCa . Epistasis analysis suggests that GON‐2 and GTL‐1 function in the IP 3 signaling pathway to regulate intestinal Ca 2+ oscillations. We postulate that GON‐2 and GTL‐1 form heteromeric ORCa channels and function to regulate IP 3 receptor activity and possibly to refill ER Ca 2+ stores. Source of research support: NIH R01 grant GM74229
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