Biology subjects

Matveev, V.

Publications and source records attributed to Matveev, V..

3 recordsLinked to original sources

bioRxiv2024

Nanophysiology Approach Revealed Diversity in Calcium Microdomains in Zebrafish Retinal Bipolar Ribbon Synapses

Rapid and high local calcium (Ca2+) signals are essential for triggering neurotransmitter release from presynaptic terminals. In specialized bipolar ribbon synapses of the retina, these local Ca2+ signals control multiple processes, including the priming, docking, and translocation of vesicles on the ribbon before exocytosis, endocytosis, and the replenishment of release-ready vesicles to the fusion sites for sustained neurotransmission. However, our knowledge about Ca2+ signals along the axis of the ribbon active zone is limited. Here, we used fast confocal quantitative dual-color ratiometric line-scan imaging of a fluorescently labeled ribbon binding peptide and Ca2+ indicators to monitor the spatial and temporal aspects of Ca2+ transients of individual ribbon active zones in zebrafish retinal rod bipolar cells (RBCs). We observed that a Ca2+ transient elicited a much greater fluorescence amplitude when the Ca2+ indicator was conjugated to a ribeye-binding peptide than when using a soluble Ca2+ indicator, and the estimated Ca2+ levels at the ribbon active zone exceeded 26 M in response to a 10-millisecond stimulus, as measured by a ribbon-bound low-affinity Ca2+ indicator. Our quantitative modeling of Ca2+ diffusion and buffering is consistent with this estimate and provides a detailed view of the spatiotemporal [Ca2+] dynamics near the ribbon. Importantly, our data demonstrates that the local Ca2+ levels may vary between ribbons of different RBCs and within the same cells. The variation in local Ca2+ signals is found to correlate with ribbon size and active zone extent. Our serial electron microscopy results provide new information about the heterogeneity in ribbon size, shape, and area of the ribbon in contact with the plasma membrane.

neuroscience↗

bioRxiv2020

Stationary Ca2+ nanodomains in the presence of buffers with two binding sites

We examine closed-form approximations for the equilibrium Ca2+ concentration near a point Ca2+ source representing a Ca2+ channel, in the presence of a mobile Ca2+ buffer with 2:1 Ca2+ binding stoichiometry. We consider buffers with two Ca2+ binding sites activated in tandem and possessing distinct binding affinities and kinetics. This allows to model the impact on Ca2+ nanodomains of realistic endogenous Ca2+ buffers characterized by cooperative Ca2+ binding, such as calretinin. The approximations we present involve a combination or rational and exponential functions, whose parameters are constrained using the series interpolation method that we recently introduced for the case of 1:1 Ca2+ buffers. We conduct extensive parameter sensitivity analysis and show that the obtained closed-form approximations achieve reasonable qualitative accuracy for a wide range of buffers Ca2+ binding properties and other relevant model parameters. In particular, the accuracy of the newly derived approximants exceeds that of the rapid buffering approximation in large portions of the relevant parameter space. STATEMENT OF SIGNIFICANCEClosed-form approximations describing equilibrium distribution of Ca2+ in the vicinity of an open Ca2+ channel proved useful for the modeling of local Ca2+ signals underlying secretory vesicle exocytosis, muscle contraction and other cell processes. Such approximations provide an efficient method for estimating Ca2+ and buffer concentrations without computationally expensive numerical simulations. However, while most biological buffers have multiple Ca2+ binding sites, much of prior modeling work considered Ca2+ dynamics in the presence of Ca2+ buffers with a single Ca2+ binding site. Here we extend modeling work on equilibrium Ca2+ nanodomains to the case of Ca2+ buffers with two binding sites, allowing to gain deeper insight into the impact of more realistic Ca2+ buffers, including cooperative buffers, on cell Ca2+ dynamics.

biophysics↗

bioRxiv2020

Efficient approximations for stationary single-channel Ca2+ nanodomains across length scales

We consider the stationary solution for the Ca2+ concentration near a point Ca2+ source describing a single-channel Ca2+ nanodomain, in the presence of a single mobile Ca2+ buffer with one-to-one Ca2+ binding. We present computationally efficient approximants that estimate stationary single-channel Ca2+ nanodomains with great accuracy in broad regions of parameter space. The presented approximants have a functional form that combines rational and exponential functions, which is similar to that of the well-known Excess Buffer Approximation and the linear approximation, but with parameters estimated using two novel (to our knowledge) methods. One of the methods involves interpolation between the short-range Taylor series of the buffer concentration and its long-range asymptotic series in inverse powers of distance from the channel. Although this method has already been used to find Pade (rational-function) approximants to single-channel Ca2+ and buffer concentration, extending this method to interpolants combining exponential and rational functions improves accuracy in a significant fraction of the relevant parameter space. A second method is based on the variational approach, and involves a global minimization of an appropriate functional with respect to parameters of the chosen approximations. Extensive parameter sensitivity analysis is presented, comparing these two methods with previously developed approximants. Apart from increased accuracy, the strength of these approximants is that they can be extended to more realistic buffers with multiple binding sites characterized by cooperative Ca2+ binding, such as calmodulin and calretinin. STATEMENT OF SIGNIFICANCEMathematical and computational modeling plays an important role in the study of local Ca2+ signals underlying vesicle exocysosis, muscle contraction and other fundamental physiological processes. Closed-form approximations describing steady-state distribution of Ca2+ in the vicinity of an open Ca2+ channel have proved particularly useful for the qualitative modeling of local Ca2+ signals. We present simple and efficient approximants for the Ca2+ concentration in the presence of a mobile Ca2+ buffer, which achieve great accuracy over a wide range of model parameters. Such approximations provide an efficient method for estimating Ca2+ and buffer concentrations without resorting to numerical simulations, and allow to study the qualitative dependence of nanodomain Ca2+ distribution on the buffers Ca2+ binding properties and its diffusivity.

biophysics↗