Cytosolic Calcium Dynamics Research Articles

Calcium and cell cycle progression: possible effects of external perturbations on cell proliferation

Exit from the phase of cellular division appears to be driven by a calcium signal that triggers a cascade of events leading to the completion of mitosis. Here we propose a model that relates the dynamics of cytosolic calcium to progression through mitosis, G1 and G2 phases of the cell cycle. To this end, the assumption has been made that the transient rise ir cytosolic calcium concentration during mitosis is induced by inositol(1,4,5)triphosphate (IP3), which in turn is released at high levels of mitosis-promoting factor (MPF). On this basis, a system of ordinary differential equations is proposed to simulate the evolution of ten cell-cycle-specific molecular species, including cyclins A and B, MPF, IP3, Ca2+, the CaMKII holoenzyme, and the ubiquitination complex. The influence on the cell proliferation capacity exerted by external perturbations, like calcium microinjections, depletion of intracellular calcium stores, electromagnetic fields, or stimulation/inhibition of different calcium currents through the plasma membrane, can be studied by appropriate modulation of the parameters involved in the signal transduction pathway.

A model of electrical activity and cytosolic calcium dynamics in vascular endothelial cells in response to fluid shear stress.

A mathematical model is proposed to describe the intracellular Ca2+ (Cai) transient and electrical activity of vascular endothelial cells (VEC) elicited by fluid shear stress (tau). The intracellular Ca2+ store of the model VEC is comprised of a Cai-sensitive (sc) and an inositol (1,4,5)-trisphosphate (IP3)-sensitive compartment (dc). The dc [Ca2+] is refilled by the sc whose [Ca2+] is the same as extracellular [Ca2+]. IP3 produced by the tau-deformed mechanoreceptors discharges the dc Ca2+ into the cytosol. The increase of cytosolic [Ca2+] induces Ca2+ release (CICR) from the sc. The raised Cai activates a Cai-activated K+ current (IK,Ca) and inhibits IP3 production. The cell membrane potential is determined by IK,Ca, voltage-dependent Na+ and K+ currents. Steady tau > 0.1 dyne/cm2 elicits a Cai transient which reaches peak value at 19-54 sec. The peak Cai varies sigmoidally with Log10(tau) with a maximal peak Cai of 150 nM at tau = 4 dynes/cm2. Step increases of tau fail to elicit a Ca2+ response in cells previously stimulated by a lower shear. The Ca2+ response gradually decreases with repetitive tau stimuli. Pulsatile shear elicits two to three times higher Cai and hyperpolarizes the cell more than steady shear of the same magnitude. The simulated Ca2+ responses to tau are quantitatively and qualitatively similar to those observed in cultured VEC. The model provides a possible explanation of why the vasodilating stimulus is greater for pulsatile flow than for nonpulsatile flow.

The dynamics of cytosolic calcium in photoreceptor cells

Analysis of the light-induced changes of cytosolic Ca2+ ([Ca2+]i) in photoreceptor cells has been taken a step further with two recently published studies. In one, changes in [Ca2+]i were measured in single detached rod outer segments from Gecko in response to various light intensities. The advances of the other are embodied in its employment of transgenic Drosophila, whose photoreceptors express a visual pigment that is insensitive to the wavelength of light used in the fluorescence imaging of [Ca2+]i. These studies provide a better basis for understanding the regulation of Ca(2+)-mediated events in photoreceptor cells.

Calculation of calcium dynamics from single wavelength fura-2 fluorescence recordings

We describe techniques for measurements of cytosolic calcium dynamics in single current- or voltage-clamped nerve cells. The calculations of calcium dynamics are based on continuous recordings of fura-2 fluorescence intensity at one excitation wavelength after an initial reference measurement at two excitation wavelengths. We show that such single wavelength recordings are not only sufficient for the calculation of Ca2+ concentrations, but also lead to a superior signal-to-noise ratio at a high temporal resolution. Moreover, this strategy diminishes requirements for the experimental setup, such as a device necessary to switch quickly between excitation filters. We have applied this approach on measurements of cytosolic free Ca2+ in single-electrode voltage-clamped CA3 pyramidal cells in hippocampal slice cultures.