IP3 receptor-mediated spatial and temporal Ca2+ signaling of the cell.

It is now revealed that "intracellular Ca2+ excitation" exists for the generation of spatial and temporal Ca2+ signals based on Ca2+ release from stores. It could be understood in analogy with electrical excitation in the cell surface, the plasma membrane. A local Ca2+ response is generated by the second messenger IP3 following agonist/receptor binding and PI turnover, corresponsing to the receptor potential or excitatory synaptic potential in neurons. The local Ca2+ response triggers a regenerative "intracellular Ca2+ spike" corresponding to the action potential. The regenerative process is the inherent property of the IP3R/Ca2+ release channel which is under positive and negative feedback controls by cytosolic and luminal Ca2+, like activation and inactivation of the voltage-gated Na+ channel. An intracellular Ca2+ spike can be induced artificially by local application of Ca2+, like induction of the action potential by a depolarizing pulse. The Ca2+ spike propagates as a spatial Ca2+ signal throughout the cell, as the action potential does. The excitation is followed by a refractory period. Repeated Ca2+ spikes are generated, depending on the magnitude of stimulus. Interval between Ca2+ spikes depends on the readiness of Ca2+ stores in terms of the sensitivity of the IP3R and extent of Ca2+ accumulation. The cycle of Ca2+ mobilization includes extracellular medium. The intracellular Ca2+ signals are thus frequency-encoded. The temporal pattern of transient Ca2+ pulses may be favorable for accomplishing cellular functions without the side effect of cell toxicity.