Calcium is a ubiquitous intracellular signalling molecule involved in regulating a range of important processes in eukaryotes. In C. elegans , calcium signalling mediated by the IP 3 receptor, encoded by the gene
itr-1 , underlies a range of ultradian rhythmic processes. In mammals, such rhythms include heart rate, blood pressure and gut peristalsis. While the molecular events underpinning circadian rhythms are increasingly well understood, ultradian rhythms remain little-studied. C. elegans is an excellent physiological model for the involvement of calcium signalling in ultradian rhythms. Muscular contractions mediating the defecation cycle are tightly regulated and occur roughly every 45 seconds, and IP 3 -mediated calcium signalling has been shown to be essential for the timing and execution of this motor program . However, key questions about the mechanism underlying the control of this rhythm remain unanswered. Our work shows how differential tissue-specific effects of IP 3 -mediated calcium signalling control multiple aspects of the motor program, specifically cycle length, rhythmicity and contraction coupling. Intestine-specific expression of
itr-1 did not rescue the cycle timing defects, suggesting that
itr-1 may not be sufficient in the intestine, in contrast to published data. Tissue-specific RNAi has indicated an additional role for
itr-1 in the muscle, where knockdown of
itr-1 resulted in short cycles. Ablation of
egl-8 (PLC?) using mutants and RNAi also showed a short cycle phenotype, suggesting that it may be functioning upstream of
itr-1 in this regulatory pathway. RNAi and mutant analysis of other plc genes has indicated that regulation of the different phenotypes controlled by
itr-1 may be divided between plc homologues. We are using imaging of calciu m dynamics in free-moving worms to determine the effect of these genetic manipulations on cellular physiology.