Abstract
The hypothalamic suprachiasmatic nucleus (SCN) is known to have a pivotal role in the generation of circadian rhythms in mammals. In mice SCN, the clock gene products BMAL1 and CLOCK are basic helix-loop-helix PAS transcription factors that form heterodimers and bind to the E-box enhancers upstream of Per and Cry genes to activate their transcription. The protein products PER and CRY form heterodimers and translocate into the nucleus to inhibit transactivation by CLOCK/BMAL1. One cycle of the molecular loop is assumed to generate a circadian cycle, called a "core loop". The core loop in the SCN may regulate diverse physiological events such as action potential firing rhythms and rhythmic secretion of arginine-vasopression and vasoactive intestinal polypeptide that may ultimately synchronize circadian behaviors. Despite the successful cloning of clock genes, the link between the gene transcription-translation cycles and oscillations in physiological activities of SCN neurons is still unclear. Recent findings that cytosolic Ca2+ concentrations oscillate with a circadian profile in SCN neurons (Ikeda et al., Neuron 38:253-63, 2003) provides a novel insight into the cellular consequences underlying physiological activity rhythms in SCN neurons. The circadian Ca2+ rhythms are driven by the release of Ca2+ from ryanodine-sensitive internal stores and resistant to the TTX-blockade of action potentials. The hypothetical interactions between Ca2+ signaling and the core loop are discussed in this presentation with regard to the importance of Ca2+ signaling in the organization of circadian rhythms in SCN neurons. [Jpn J Physiol 54 Suppl:S6 (2004)]
