The nephron-arterial network and its interactions.

Tubuloglomerular feedback and the myogenic mechanism form an ensemble in renal afferent arterioles that regulate single-nephron blood flow and glomerular filtration. Each mechanism generates a self-sustained oscillation, the mechanisms interact, and the oscillations synchronize. The synchronization generates a bimodal electrical signal in the arteriolar wall that propagates retrograde to a vascular node, where it meets similar electrical signals from other nephrons.

Architecture of the rat nephron-arterial network: analysis with micro-computed tomography.

Among solid organs, the kidney's vascular network stands out, because each nephron has two distinct capillary structures in series and because tubuloglomerular feedback, one of the mechanisms responsible for blood flow autoregulation, is specific to renal tubules. Tubuloglomerular feedback and the myogenic mechanism, acting jointly, autoregulate single-nephron blood flow. Each generates a self-sustained periodic oscillation and an oscillating electrical signal that propagates upstream along arterioles.

Multinephron dynamics on the renal vascular network.

Tubuloglomerular feedback (TGF) and the myogenic mechanism combine in each nephron to regulate blood flow and glomerular filtration rate. Both mechanisms are nonlinear, generate self-sustained oscillations, and interact as their signals converge on arteriolar smooth muscle, forming a regulatory ensemble. Ensembles may synchronize.

Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy.

This paper presents a nonivasive approach to study redox state of reduced cytochromes c, c1 and b of complexes II and III in mitochondria of live cardiomyocytes by means of Raman microspectroscopy. For the first time with the proposed approach we perform studies of rod- and round-shaped cardiomyocytes, representing different morphological and functional states. Raman mapping and cluster analysis reveal that these cardiomyocytes differ in the amounts of reduced cytochromes c, c1 and b.

Nephron blood flow dynamics measured by laser speckle contrast imaging.

Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations.

Coupling-induced complexity in nephron models of renal blood flow regulation.

Tubular pressure and nephron blood flow time series display two interacting oscillations in rats with normal blood pressure. Tubuloglomerular feedback (TGF) senses NaCl concentration in tubular fluid at the macula densa, adjusts vascular resistance of the nephron's afferent arteriole, and generates the slower, larger-amplitude oscillations (0.02-0.

Novel chiroptical analysis of hemoglobin by surface enhanced resonance Raman optical activity spectroscopy.

The metalloprotein hemoglobin (Hb) was studied using surface enhanced resonance Raman spectroscopy (SERRS) and surface enhanced resonance Raman optical activity (SERROA). The SERROA results are analyzed and compared with the SERRS, and the later to the resonance Raman (RRS) performed on Hb. The SERRS measurements careful optimization, with respect to the concentration and volume ratio of the analyte to colloids, enables for the first time SERROA of this molecule.

New insight into erythrocyte through in vivo surface-enhanced Raman spectroscopy.

The article presents a noninvasive approach to the study of erythrocyte properties by means of a comparative analysis of signals obtained by surface-enhanced Raman spectroscopy (SERS) and resonance Raman spectroscopy (RS). We report step-by-step the procedure for preparing experimental samples containing erythrocytes in their normal physiological environment in a mixture of colloid solution with silver nanoparticles and the procedure for the optimization of SERS conditions to achieve high signal enhancement without affecting the properties of living erythrocytes. By means of three independent techniques, we demonstrate that under the proposed conditions a colloid solution of silver nanoparticles does not affect the properties of erythrocytes.

Electrotonic vascular signal conduction and nephron synchronization.

Tubuloglomerular feedback (TGF) and the myogenic mechanism control afferent arteriolar diameter in each nephron and regulate blood flow. Both mechanisms generate self-sustained oscillations, the oscillations interact, TGF modulates the frequency and amplitude of the myogenic oscillation, and the oscillations synchronize; a 5:1 frequency ratio is the most frequent. TGF oscillations synchronize in nephron pairs supplied from a common cortical radial artery, as do myogenic oscillations.

Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study.

We describe how phase-modulation laser interference microscopy and wavelet analysis can be applied to noninvasive nonstained visualization and study of the structural and dynamical properties of living cells. We show how phase images of erythrocytes can reveal the difference between various erythrocyte forms and stages of hemolysis and how phase images of neurons reveal their complex intracellular structure. Temporal variations of the refractive index are analyzed to detect cellular rhythmic activity on different time scales as well as to uncover interactions between the cellular processes.

Synchronization among mechanisms of renal autoregulation is reduced in hypertensive rats.

We searched for synchronization among autoregulation mechanisms using wavelet transforms applied to tubular pressure recordings in nephron pairs from the surface of rat kidneys. Nephrons have two oscillatory modes in the regulation of their pressures and flows: a faster (100-200 mHz) myogenic mode, and a slower (20-40 mHz) oscillation in tubuloglomerular feedback (TGF). These mechanisms interact; the TGF mode modulates both the amplitude and the frequency of the myogenic mode.

Noise controlled synchronization in potassium coupled neural models.

The paper applies biologically plausible models to investigate how noise input to small ensembles of neurons, coupled via the extracellular potassium concentration, can influence their firing patterns. Using the noise intensity and the volume of the extracellular space as control parameters, we show that potassium induced depolarization underlies the formation of noise-induced patterns such as delayed firing and synchronization. These phenomena are associated with the appearance of new time scales in the distribution of interspike intervals that may be significant for the spatio-temporal oscillations in neuronal ensembles.

Vascular coupling induces synchronization, quasiperiodicity, and chaos in a nephron tree.

The paper presents a study of synchronization phenomena in a system of 22 nephrons supplied with blood from a common cortical radial artery. The nephrons are assumed to interact via hemodynamic and vascularly propagated coupling, both mediated by vascular connections. Using anatomic and physiological criteria, the nephrons are divided into groups: cortical nephrons and medullary nephrons with short, intermediate and long Henle loops.

Application of wavelet-based tools to study the dynamics of biological processes.

The article makes use of three different examples (sensory information processing in the rat trigeminal complex, intracellular interaction in snail neurons and multimodal dynamics in nephron autoregulation) to demonstrate how modern approaches to time-series analysis based on the wavelet-transform can provide information about the underlying complex biological processes.

Neural synchronization via potassium signaling.

Using a relatively simple model we examine how variations of the extracellular potassium concentration can give rise to synchronization of two nearby pacemaker cells. With the volume of the extracellular space and the rate of potassium diffusion as control parameters, the dual nature of this resource-mediated coupling is found to be responsible for the coexistence of competing patterns of in- and anti-phase synchronization between identical cells. Cell heterogeneity produces significant modifications of the dynamical regimes in the control parameter plane.

Oscillator clustering in a resource distribution chain.

The paper investigates the special clustering phenomena that one can observe in systems of nonlinear oscillators that are coupled via a shared flow of primary resources (or a common power supply). This type of coupling, which appears to be quite frequent in nature, implies that one can no longer separate the inherent dynamics of the individual oscillator from the properties of the coupling network. Illustrated by examples from microbiological population dynamics, renal physiology, and electronic oscillator theory, we show how competition for primary resources in a resource distribution chain leads to a number of new generic phenomena, including partial synchronization, sliding of the synchronization region with the resource supply, and coupling-induced inhomogeneity.

Mechanism-based modeling of complex biomedical systems.

Mechanism-based modeling is an approach in which the physiological, pathological and pharmacological processes of relevance to a given problem are represented as directly as possible. This approach allows us (i) to test whether assumed hypotheses are consistent with observed behaviour, (ii) to examine the sensitivity of a system to parameter variation, (iii) to learn about processes not directly amenable to experimentation, and (iv) to predict system behavior under conditions not previously experienced. The paper illustrates different aspects of the application of mechanism-based modeling through three different examples of relevance to the treatment of diabetes and hypertension: subcutaneous absorption of insulin, pulsatile insulin secretion in normal young persons, and synchronization of the pressure and flow regulation in neighbouring nephrons.

Nonlinear interactions in renal blood flow regulation.

We have developed a model of tubuloglomerular feedback (TGF) and the myogenic mechanism in afferent arterioles to understand how the two mechanisms are coupled. This paper presents the model. The tubular model predicts pressure, flow, and NaCl concentration as functions of time and tubular length in a compliant tubule that reabsorbs NaCl and water; boundary conditions are glomerular filtration rate (GFR), a nonlinear outflow resistance, and initial NaCl concentration.

Frequency encoding in renal blood flow regulation.

With a model of renal blood flow regulation, we examined consequences of tubuloglomerular feedback (TGF) coupling to the myogenic mechanism via voltage-gated Ca channels. The model reproduces the characteristic oscillations of the two mechanisms and predicts frequency and amplitude modulation of the myogenic oscillation by TGF. Analysis by wavelet transforms of single-nephron blood flow confirms that both amplitude and frequency of the myogenic oscillation are modulated by TGF.

Synchronization phenomena in nephron-nephron interaction.

Experimental data for tubular pressure oscillations in rat kidneys are analyzed in order to examine the different types of synchronization that can arise between neighboring functional units. For rats with normal blood pressure, the individual unit (the nephron) typically exhibits regular oscillations in its tubular pressure and flow variations. For such rats, both in-phase and antiphase synchronization can be demonstrated in the experimental data.