Astrocyte calcium signaling: Interplay between structural and dynamical patterns.

Inspired by calcium activity in astrocytes, which is different in the cell body and thick branches on the one hand and thin branchlets and leaflets on the other hand, we formulate a concept of spatially partitioned oscillators. These are inhomogeneous media with regions having different excitability properties, with a global dynamics governed by spatial configuration of such regions. Due to a high surface-to-volume ratio, calcium dynamics in astrocytic leaflets is dominated by transmembrane currents, while somatic calcium dynamics relies on exchange with intracellular stores, mediated by IP 3 , which is in turn synthesized in the space nearby the plasma membrane. Reciprocal coupling via diffusion of calcium and IP 3 between the two regions makes the spatial configuration an essential contributor to overall dynamics. Due to these features, the mechanisms governing the pattern formation of calcium dynamics differ from classical excitable systems with noise or from networks of clustered oscillators. We show how geometrical inhomogeneity can play an ordering role allowing for stable scenarios for calcium wave initiation and propagation.

New nanocomposites for SERS studies of living cells and mitochondria.

A great enhancement in Raman scattering (SERS) from heme-containing submembrane biomolecules inside intact erythrocytes and functional mitochondria is demonstrated for the first time using silver-silica beads prepared using a new method involving aerosol pyrolysis with aqueous diamminesilver(i) hydroxide as a unique source of plasmonic nanoparticles for SiO2 microspheres. The recorded SERS spectra reveal a set of characteristic peaks at 750, 1127, 1170, 1371, 1565, 1585 and 1638 cm-1, resulting from the normal group vibrations of the pyrrole rings, methine bridges and side radicals in the heme molecules. The SERS spectra of functional mitochondria are sensitive to the activity of the mitochondrial electron transport chain, thus making the method a novel label-free approach to monitor the redox state and conformation of cytochromes in their natural cell environment. The developed nanocomposites are highly suitable for the analysis of biological objects due to their robust synthesis and superior spatial and temporal signal reproducibility, which was preserved for a period of at least one year.

Conducted vasoreactivity: the dynamical point of view.

Conducted vasodilation is part of the physiological response to increasing metabolic demand of the tissue. Similar responses can be elicited by focal electrical or chemical stimulation. Some evidence suggests an endothelial pathway for nondecremental transmission of hyperpolarizing pulses. However, the underlying mechanisms are debated. Here, we focus on dynamical aspects of the problem hypothesizing the existence of a bistability-powered mechanism for regenerative pulse transmission along the endothelium. Bistability implies that the cell can have two different stable resting potentials and can switch between those states following an appropriate stimulus. Bistability is possible if the current-voltage curve is N shaped instead of monotonically increasing. Specifically, the presence of an inwardly rectifying potassium current may provide the endothelial cell with such properties. We provide a theoretical analysis as well as numerical simulations of both single- and multiunit bistable systems mimicking endothelial cells to investigate the self-consistence and stability of the proposed mechanism. We find that the individual cell may switch readily between two stable potentials. An array of coupled cells, however, as found in the vascular wall, requires a certain adaptation of the membrane currents after a switch, in order to switch back. Although the formulation is generic, we suggest a combination of specific membrane currents that could underlie the phenomenon.

Dynamics of nephron-vascular network.

The paper presents a modeling study of the spatial dynamics of a nephro-vascular network consisting of individual nephrons connected via a tree-like vascular branching structure. We focus on the effects of nonlinear mechanisms that are responsible for the formation of synchronous patterns in order to learn about processes not directly amenable to experimentation. We demonstrate that: (i) the nearest nephrons are synchronized in-phase due to a vascular propagated electrical coupling, (ii) the next few branching levels display a formation of phase-shifted patterns due to hemodynamic coupling and mode elimination, and (iii) distantly located areas show asynchronous behavior or, if all nephrons and branches are perfectly identical, an infinitely long transient behavior. These results contribute to the understanding of mechanisms responsible for the highly dynamic and limited synchronization observed among groups of nephrons despite of the fairly strong interaction between the individual units.

Functional modeling of the shift in cellular calcium dynamics at the onset of synchronization in smooth muscle cells.

In the present paper we address the nature of synchronization properties found in populations of mesenteric artery smooth muscle cells. We present a minimal model of the onset of synchronization in the individual smooth muscle cell that is manifested as a transition from calcium waves to whole-cell calcium oscillations. We discuss how different types of ion currents may influence both amplitude and frequency in the regime of whole-cell oscillations. The model may also explain the occurrence of mixed-mode oscillations and chaotic oscillations frequently observed in the experimental system.

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance.

The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization.

Dynamical patterns of calcium signaling in a functional model of neuron-astrocyte networks.

We propose a functional mathematical model for neuron-astrocyte networks. The model incorporates elements of the tripartite synapse and the spatial branching structure of coupled astrocytes. We consider glutamate-induced calcium signaling as a specific mode of excitability and transmission in astrocytic-neuronal networks. We reproduce local and global dynamical patterns observed experimentally.

The effect of L-NAME on intra- and inter-nephron synchronization.

Kidney autoregulation involves complicated intra- and inter-nephron synchronization phenomena among oscillatory modes produced, respectively, by the tubuloglomerular feedback (TGF) mechanism and by the myogenic regulation of the afferent arteriolar blood flow. The present study aims at examining to what extent these phenomena are reflected in the overall blood flow to the kidney and how they are affected by intravenous administration of nitro-l-arginine-methyl-ester (L-NAME), a potent NO synthesis inhibitor. Wavelet analysis is applied to detect rhythmic activity at the level of the renal artery and compare the observed fluctuations with blood flow variations recorded from efferent arterioles of individual nephrons. We show that administration of L-NAME increases the gain in both the TGF and the myogenic oscillations, and that both normotensive and hypertensive rats demonstrate reduced stability of the various rhythms. This implies that L-NAME, besides strengthening the gain in the individual feedback mechanisms, also causes more frequent transitions among the various synchronization states. In a broader perspective the purpose of the study is to demonstrate the significance of complex dynamic phenomena in the normal regulation of physiological systems as well as in their response to drugs.

Non-invasive study of nerve fibres using laser interference microscopy.

This paper presents the results of a laser interference microscopy study of the morphology and dynamical properties of myelinated nerve fibres. We describe the principles of operation of the phase-modulated laser interference microscope and show how this novel technique allows us to obtain information non-invasively about the internal structure of different regions of a nerve fibre. We also analyse the temporal variations in the internal optical properties in order to detect the rhythmic activity in the nerve fibre at different time scales and to shed light on the underlying biological processes. We observe pronounced frequencies in the dynamics of the optical properties and suggest that the oscillatory modes have similar origin in different regions, but different strengths and mutual modulation properties.

Characterizing multimode interaction in renal autoregulation.

The purpose of this paper is to demonstrate how modern statistical techniques of non-stationary time-series analysis can be used to characterize the mutual interaction among three coexisting rhythms in nephron pressure and flow regulation. Besides a relatively fast vasomotoric rhythm with a period of 5-8 s and a somewhat slower mode arising from an instability in the tubuloglomerular feedback mechanism, we also observe a very slow mode with a period of 100-200 s. Double-wavelet techniques are used to study how the very slow rhythm influences the two faster modes. In a broader perspective, the paper emphasizes the significance of complex dynamic phenomena in the normal and pathological function of physiological systems and discusses how simulation methods can help to understand the underlying biological mechanisms. At the present there is no causal explanation of the very slow mode. However, vascular oscillations with similar frequencies have been observed in other tissues.