Spatial and temporal aspects of cellular calcium signaling

Abstract

Cytosolic Ca2+ signals are often organized in complex temporal and spatial patterns, even under conditions of sustained stimulation. In this review we discuss the mechanisms and physiological significance of this behavior in nonexcitable cells, in which the primary mechanism of Ca2+ mobilization is through (1,4,5)IP3-dependent Ca2+ release from intracellular stores. Oscillations of cytosolic free Ca2+ ([Ca2+]i) are a common form of temporal organization; in the spatial domain, these [Ca2+]i oscillations may take the form of [Ca2+]i waves that propagate throughout the cell or they may be restricted to specific subcellular regions. These patterns of Ca2+ signaling result from the limited range of cytoplasmic Ca2+ diffusion and the feedback regulation of the pathways responsible for Ca2+ mobilization. In addition, the spatial organization of [Ca2+]i changes appears to depend on the strategic distribution of Ca2+ stores within the cell. One type of [Ca2+]i oscillation is baseline spiking, in which discrete [Ca2+]i spikes occur with a frequency, but not amplitude, that is determined by agonist dose. Most current evidence favors a model in which baseline [Ca2+]i spiking results from the complex interplay between [Ca2+]i and (1,4,5)IP3 in regulating the gating of (1,4,5)IP3-sensitive intracellular Ca2+ channels. Sinusoidal [Ca2+]i oscillations represent a mechanistically distinct type of temporal organization, in which agonist dose regulates the amplitude but has no effect on oscillation frequency. Sinusoidal [Ca2+]i oscillations can be explained by a negative feedback effect of protein kinase C on the generation of (1,4,5)IP3 at the level of phospholipase C or its activating G-protein. The physiological significance of [Ca2+]i oscillations and waves is becoming more established with the observation of this behavior in intact tissues and by the recognition of Ca2+-dependent processes that are adapted to respond to frequency-modulated oscillatory [Ca2+]i signals. In some cells, these [Ca2+]i signals are targeted to control processes in limited cytoplasmic domains, and in other systems [Ca2+]i waves can be propagated through gap junctions to coordinate the function of multicellular systems.

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

“…In order to assess the effects of morin hydrate on the functionality of the in vitro neural network, we conducted calcium signalling assay, in the absence and presence of morin hydrate. Calcium oscillations were visualized by fluo‐8‐AM staining, as spontaneous and rhythmic spikes of fluorescent signals 24. As expected, morin hydrate treatment greatly increased the number of neurons with calcium oscillation (Fig.…”

Unique kinetics of nicotinic acid–adenine dinucleotide phosphate (NAADP) binding enhance the sensitivity of NAADP receptors for their ligand

“…The structurally and functionally related ryanodine receptors [4], initially characterized in muscle cells, are also widespread and are gated by cADP-ribose (cADPR) [5,6]. Both IP $ and ryanodine receptors are regulated by Ca# + [7], a property that probably underlies the complex spatial and temporal nature of cytosolic Ca# + signals typically observed in response to physiological stimuli [8].…”

Regulation of cerebellar Ins(1,4,5)P3 receptor by interaction between Ins(1,4,5)P3 and Ca2+

“…For InsP $ -dependent Ca# + signals, regulation at the level of InsP $ R is thought to have a major role. Current evidence supports a mechanism in which the spikes in cytosolic Ca# + concentration reflect a positive feedback effect on InsP $ R quickly followed by its inactivation [8]. In cerebellum, as in most cells and tissues studied so far, InsP $ and Ca# + seem to be the most important determinants of channel activity.…”

“…These interactions are probably important elements in the fine regulation of the InsP $ R, which is known to have a key role in Ca# + signal organization [8].…”