A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons

Abstract

], reversibly abolished the rhythmic expression of Per1. In addition, the amplitude of Per1 expression was markedly decreased by voltage-gated Ca 2ϩ channel antagonists. A similar result was observed for mouse Per1 and PER2. Together, these results strongly suggest that a transmembrane Ca 2ϩ flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca 2ϩ influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function.

Depolarization and Neurotransmitter Regulation of Vasopressin Gene Expression in the Rat Suprachiasmatic NucleusIn Vitro

“…The effect of potassium depolarization to increase VP gene transcription in TTX that was blocked by inhibitors of calcium ion influx through voltage-gated calcium channels (Fig. 9, Cd, nimodipine) is consistent with this hypothesis and with reports describing voltage-gated calcium channels as an important factor in the regulation of circadian rhythms in the SCN (Pennartz et al, 2002;Lundkvist et al, 2005;Pakhotin et al, 2006). Inhibition by the CaM general protein kinase inhibitor (KN62) but not by a specific CaM protein kinase II inhibitor (KN93) suggests that this signal transduction pathway might use CaM IV (Obrietan et al, 2002).…”

“…Therefore, these two mechanisms are not entirely independent. Nevertheless, it is interesting that the loss of the VPAC2 receptor causes substantial hyperpolarization in SCN neurons and a correlated decrease in mPer gene expression (Lundkvist et al, 2005). There are two mechanisms by which depolarization can influence the VP neurons, synaptic and direct electrical (spike) activity.…”

Gastrin-Releasing Peptide Promotes Suprachiasmatic Nuclei Cellular Rhythmicity in the Absence of Vasoactive Intestinal Polypeptide-VPAC2Receptor Signaling

“…Activation of the BB 2 receptor produces primarily excitatory responses in cells throughout the rodent SCN (Piggins and Rusak, 1993;Piggins et al, 1994Piggins et al, , 2005Reynolds and Pinnock, 1997;Cutler et al, 2003; our study) and, like VIP, GRP is believed to be important for communicating phase information between neurons within the circadian clock (Antle et al, 2005). Interestingly, GRP, which promotes cellular rhythmicity in the Vipr2 Ϫ/Ϫ SCN, also increases the amplitude of such rhythms compared with those observed in untreated slices, supporting previous suggestions that a threshold of neuronal activity is required to sustain clock function (Van den Pol and Obrietan, 2002;Nitabach et al, 2002;Yamaguchi et al, 2003;Lundkvist et al, 2005). Surprisingly, another agent that excites the majority of SCN neurons, NMDA (Schmahl and Bohmer, 1997;Cutler et al, 2003), does not increase the amplitude or proportion of cells expressing rhythms in the Vipr2 Ϫ/Ϫ SCN.…”

Role of Na+/Ca2+exchanger in Ca2+homeostasis in rat suprachiasmatic nucleus neurons

“…In the rat SCN, TTX eliminates the day-night variation in [Ca 2ϩ ] i (Colwell 2000) or similarly lowers baseline Ca 2ϩ ratio between day and night (Irwin and Allen 2009), suggesting an important contribution of action potential (voltage)-dependent transmembrane Ca 2ϩ influx to basal [Ca 2ϩ ] i . Indeed, transmembrane Ca 2ϩ influx appears to be required for maintaining rhythmicity of the clock gene per1 in the rat SCN and of both per1 gene and PER2 protein in the mouse SCN (Lundkvist et al 2005). Furthermore, glutamate-mediated phase shifts during the night critically depend on Ca 2ϩ influx via voltage-dependent Ca 2ϩ channels (Irwin and Allen 2007;Kim et al 2005) as well as ryanodine receptor-mediated Ca 2ϩ signaling (Ding et al 1998;Gillette and Mitchell 2002).…”