TY - JOUR T1 - Highly Ca2+-selective TRPM channels regulate IP3-dependent oscillatory Ca2+ signaling in the C. elegans intestine. AU - Xing,Juan, AU - Yan,Xiaohui, AU - Estevez,Ana, AU - Strange,Kevin, PY - 2008/2/27/pubmed PY - 2008/6/17/medline PY - 2008/2/27/entrez SP - 245 EP - 55 JF - The Journal of general physiology JO - J Gen Physiol VL - 131 IS - 3 N2 - Posterior body wall muscle contraction (pBoc) in the nematode Caenorhabditis elegans occurs rhythmically every 45-50 s and mediates defecation. pBoc is controlled by inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ oscillations in the intestine. The intestinal epithelium can be studied by patch clamp electrophysiology, Ca2+ imaging, genome-wide reverse genetic analysis, forward genetics, and molecular biology and thus provides a powerful model to develop an integrated systems level understanding of a nonexcitable cell oscillatory Ca2+ signaling pathway. Intestinal cells express an outwardly rectifying Ca2+ (ORCa) current with biophysical properties resembling those of TRPM channels. Two TRPM homologues, 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 here that GON-2 and GTL-1 are both required for maintaining rhythmic pBoc and intestinal Ca2+ oscillations. Loss of GTL-l and GON-2 function inhibits I(ORCa) approximately 70% and approximately 90%, respectively. I(ORCa) is undetectable in gon-2;gtl-1 double mutant cells. These results demonstrate that (a) both gon-2 and gtl-1 are required for ORCa channel function, and (b) GON-2 and GTL-1 can function independently as ion channels, but that their functions in mediating I(ORCa) are interdependent. I(ORCa), I(GON-2), and I(GTL-1) have nearly identical biophysical properties. Importantly, all three channels are at least 60-fold more permeable to Ca2+ than Na+. Epistasis analysis suggests that GON-2 and GTL-1 function in the IP3 signaling pathway to regulate intestinal Ca2+ oscillations. We postulate that GON-2 and GTL-1 form heteromeric ORCa channels that mediate selective Ca2+ influx and function to regulate IP3 receptor activity and possibly to refill ER Ca2+ stores. SN - 1540-7748 UR - https://www.unboundmedicine.com/medline/citation/18299395/Highly_Ca2+_selective_TRPM_channels_regulate_IP3_dependent_oscillatory_Ca2+_signaling_in_the_C__elegans_intestine_ L2 - https://rupress.org/jgp/article-lookup/doi/10.1085/jgp.200709914 DB - PRIME DP - Unbound Medicine ER -