Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Xing, J. Articles by Strange, K. PubMed PubMed Citation Articles by Xing, J. Articles by Strange, K. Social Bookmarking                      What's this?

Departments of Anesthesiology, Molecular Physiology and Biophysics, and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232

Correspondence to Kevin Strange: kevin.strange{at}vanderbilt.edu

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 70% and 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.

Abbreviations used in this paper: CICR, Ca²⁺-induced Ca²⁺ release; CRAC, Ca²⁺ release–activated Ca²⁺; dsRNA, double-stranded RNA; IP₃, inositol-1,4,5-trisphosphate; ORCa, outwardly rectifying Ca²⁺; pBoc, posterior body wall muscle contraction; SERCA, sarco/endoplasmic reticulum Ca²⁺ ATPase; SOCC, store-operated Ca²⁺ channel.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Xing, X. Yan, A. Estevez, and K. Strange Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine J. Cell Biol., March 5, 2008; 180(5): i18 - i18. [Full Text]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents