C. elegans neuronal system constitutes the ideal framework for studying simple, yet realistic, neuronal activity, since the whole nervous system is fully characterized with respect to the exact number of neurons and the neuronal connections. Most recent efforts are devoted to investigate and clarify the signal processing and functional connectivity, which are at the basis of sensing mechanisms, signal transmission, and motor control. In this framework, a refined modelof whole neuron dynamics constitutes a key ingredient to describe the electrophysiological processes, both at thecellular and at the network scale. In this work, we present Hodgkin-Huxley-based models of ion channels dynamics black, built on data available both from C. elegans and from other organisms, expressing homologous channels. We combine these channel models to simulate the electrical activity oftwo among the most studied neurons in C. elegans, which display prototypical dynamics of neuronal activation, the chemosensory AWC^ON and the motor neuron RMD. Our model properly describes the regenerative responses of the two cells. We analyze in detail the role of ion currents, both in wild type and in in silico knockout neurons. Moreover, we specifically investigate the behavior of RMD, identifying a heterogeneous dynamical response which includes bistable regimes and sustained oscillations. We are able to assess the critical role of T-type calcium currents, carried by CCA-1 channels, and leakage currents in the regulation of RMD response. Overall, our results provide new insights in the activity of key C. elegans neurons. The developed mathematical framework constitute a basis for single-cell and neuronal networks analyses, opening new scenarios in the in silico modeling of C. elegans neuronal system.

Coordinated insulin secretion is controlled by electrical coupling of pancreatic β -cells due to connexin-36 gap junctions. Gap junction coupling not only synchronizes the heterogeneous β -cell population, but can also modify the electrical behavior of the cells. These phenomena have been widely studied with mathematical models based on data from mouse β -cells. However, it is now known that human β -cell electrophysiology shows important differences to its rodent counterpart, and although human pancreatic islets express connexin-36 and show evidence of β -cell coupling, these aspects have been little investigated in human β -cells. Here we investigate theoretically, the gap junction coupling strength required for synchronizing electrical activity in a small cluster of cells simulated with a recent mathematical model of human β -cell electrophysiology. We find a lower limit for the coupling strength of approximately 20 pS (i.e., normalized to cell size, ∼2 pS pF ⁻¹ ) below which spiking electrical activity is asynchronous. To confront this theoretical lower bound with data, we use our model to estimate from an experimental patch clamp recording that the coupling strength is approximately 100–200 pS (10–20 pS pF ⁻¹ ), similar to previous estimates in mouse β -cells. We then investigate the role of gap junction coupling in synchronizing and modifying other forms of electrical activity in human β -cell clusters. We find that electrical coupling can prolong the period of rapid bursting electrical activity, and synchronize metabolically driven slow bursting, in particular when the metabolic oscillators are in phase. Our results show that realistic coupling conductances are sufficient to promote synchrony in small clusters of human β -cells as observed experimentally, and provide motivation for further detailed studies of electrical coupling in human pancreatic islets.

Using the FitzHugh-Nagumo equations to represent the oscillatory electrical behavior of $\beta$-cells, we develop a coupled oscillator network model with cubic lattice topology, showing that the emergence of pacemakers or hubs in the system can be viewed as a natural consequence of oscillator population diversity. The optimal hub to nonhub ratio is determined by the position of the diversity-induced resonance maximum for a given set of FitzHugh-Nagumo equation parameters and is predicted by the model to be in a range that is fully consistent with experimental observations. The model also suggests that hubs in a $\beta$-cell network should have the ability to “switch on” and “off” their pacemaker function. As a consequence, their relative amount in the population can vary in order to ensure an optimal oscillatory performance of the network in response to environmental changes, such as variations of an external stimulus.

We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.

This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q₁₀ and Moore factors are used to describe thermo-electric feedback in a 10° range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra, and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis.