Ca²⁺ talks a lot for the circadian clock system

Abstract

The hypothalamic suprachiasmatic nucleus (SCN) has a pivotal role in the mammalian circadian clock. SCN neurons generate circadian rhythms in action potential firing frequencies and neurotransmitter release, and the core oscillation is thought to be driven by “clock gene” transcription-translation feedback loops. Various neurotransmitters, receptors and second messenger systems have been proposed for the signal transduction mechanisms in SCN neurons. Among these, glutamate-induced Ca²⁺ flux is one of the most important pathways to regulate the circadian oscillations. Cytosolic Ca²⁺ mobilization followed by receptor stimulation thus has been studied extensively in SCN neurons, whereas contribution of steady-state cytosolic Ca²⁺ levels to the rhythm generation was unclear. Therefore, we challenged ultra long-term (up to 2 weeks) Ca²⁺ imaging experiment in cultured SCN neurons with a Ca²⁺ indicator protein, Yellow Cameleon 2.1, and found robust circadian rhythms in the cytoplasmic concentration of Ca²⁺ (Ikeda et al., Neuron 38:252-263, 2003). The circadian Ca²⁺ rhythms are driven by the release of Ca²⁺ from ryanodine-sensitive internal stores and resistant to the blockade of action potentials. These results raise the possibility that clock gene translation/transcription loops may interact with the autonomous Ca²⁺ oscillations in the production of circadian rhythms in SCN neurons (Ikeda, Trends Neurosci 26:654, 2003), and thus demonstrate that Ca²⁺ is a key intracellular messenger for the circadian clock system. [Jpn J Physiol 55 Suppl:S19 (2005)]