Calcium oscillations and autowaves in cells

The experiments were carried out on cultures of various cells. A fluorescent probe Fura-2 was used to detect [Ca²⁺]_i changes. An inverted microscope Leica DMI6000B was used to register Fura-2 fluorescence.

Activation of many receptors causes an intracellular signal in the form of Ca²⁺ oscillations. Recording of oscillations in individual cells of the same type showed that the same receptor induces oscillations of different frequencies and amplitudes, and this leads to the expression of different genes. The recording of oscillations in large cells showed that these oscillations are undamped calcium autowaves that propagate along the surface of the endoplasmic reticulum (ER). The mechanism of these auto waves was studied and it was shown that an Ca²⁺ concentration increase at some point activates a Ca²⁺-dependent Ca²⁺ release from the ER and generates a wave. The same calcium acts as a periodically appearing inhibitor, which closes the channel, interacting with calmodulin. It has also been demonstrated that autowaves can occur when intracellular signaling systems are activated without the participation of receptors. Thus, the activation of adenylate cyclase caused the chaotic appearance of microwaves in various parts of the cell, the source of which was a local calcium increase, which was followed by the predominance of a single pacemaker source and the appearance of a macro wave. It has been shown that the Ca²⁺ waves are involved in intercellular communication. The intracellular Ca²⁺ wave causes the pulse release of messengers that activate the calcium-mobilizing receptor on neighboring cells. Thus, the intracellular Ca²⁺ wave is transformed into an autowave of extracellular messenger. The voltage-dependence of ionic channels that determine the electrical excitability of nerve cells allows for the existence of a mode of "synchronous" excitation of all neurons in the network. It takes place under the effect of stochastic potential changes in conditions when all neurons are switched to a mode close to excitation. Moreover, if the composition of voltage-generating channels includes low-threshold Ca²⁺ channels, then in this case, neurons periodically generate not one, but a burst of action potentials (AP). This mode of synchronous activity is normally realized to activate the growth of dendrites and form synaptic contacts between neurons. In the adult brain, the mode is a sign of pathology and appears in epilepsy, ischemic strokes and other brain injuries. The mode has all indications of an autowave: the undamped oscillations, the voltage-dependent of Ca²⁺ channels, the gradient of Ca²⁺ ions as an energy source. Taking into account the autowave nature of calcium oscillations in neurons allows for more intentional control of excitation during the development of the neuronal network, epilepsy and strokes.