The laboratory of biophysical and computer modelling of biological electrical signals
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The generation and transmission of electrical signals and
pulses in biological cells and tissues is studied in the field
of bioelectricity. Our lab main research goal is to model such signals, from the
microcellular ion channel currents to the macroscopic action potentials
and propagating electrical waves. We focus on the cardiac electrical
activity as well as on transmission along neurons, in the aim of
characterizing abnormal patterns that may lead e.g. to cardiac
arrhythmias or neurological pathologies. The following are examples
from two recent studies.
Electrotonic Myofibroblast-to-Myocyte Coupling Increases Propensity to Reentrant Arrhythmias in Two-Dimensional Cardiac Monolayers In
pathological conditions such as ischemic cardiomyopathy and heart
failure, differentiation of fibroblasts into myofibroblasts may result
in myocyte-fibroblast electrical coupling via gap junctions (Figure
1).
 We
hypothesized that myofibroblast proliferation and increased
heterocellular coupling significantly alter two-dimensional cardiac
wave propagation and reentry dynamics. Co-cultures of myocytes andmyofibroblasts from neonatal rat
ventricles were optically mapped using a voltage-sensitive dye during
pacing and sustained reentry. The myofibroblast/myocyte ratio was
changed systematically, and junctional coupling of the myofibroblasts was reduced or increased using silencing RNAi or adenoviral overexpression of Cx43, respectively (Figure 2). Numerical simulat ions
in two-dimensional models were used to quantify the effects of
heterocellular coupling on conduction velocity (CV) and reentry
dynamics. In both simulations and experiments, reentry frequency and CV
diminished with larger myofibroblast/myocyte area ratios; complexity of
propagation increased, resulting in wave fractionation and reentry
multiplication (Figure
3). The relationship between CV and coupling was biphasic: an initial
decrease in CV was followed by an increase as heterocellular coupling
increased. Low heterocellular coupling resulted in fragmented and wavy
wavefronts; at high coupling wavefronts became smoother. The results
provide novel insight into the mechanisms whereby electrical myocyte-myofibroblast interactions modify wave propagation and the propensity to reentrant arrhythmias. For further details, the published article can be found here in a PDF format:  PDF ArticlePersistent Reflection Underlies Ectopic Activity in Multiple Sclerosis A Numerical Study Ectopic activity in multiple sclerosis (MS) patients
has been traditionally attributed to hyperexcitability of the
demyelinated axon segments. Here we propose that the same outcome may
be the result of persistent reflection – the continuous
reactivation of the axonal nodes that limit a demyelinated internodal
segment. Using computer simulations we studied the patterns of impulse
propagation for a wide range of electrophysiological conditions. In
uniformly myelinated fibers, increasing the temperature enabled
successful propagation with no blocks in more severe conditions of
demyelination. Short-lived reflected action potentials were formed for
temperatures higher than T=303K, and for internodal axonal widths no
larger than rs~7?m. Persistent (resonant
and transient) reflections appeared in the case of focally demyelinated
fibers, and only within a narrow range of parameters (T=303K, rs within
5.08-5.13?m), Figure 4. Resonant reflection reached steady state in
ionic currents within 15ms, and was characterized with a very high
sensitivity of the activation frequency to rs, with frequencies within
300-550 Hz. We conclude that persistent reflection is a possible
mechanism for ectopic activity in MS patients, being more prominent in
higher temperatures and severe axonal demyelination. Eliminating these
symptoms may be addressed by cooling the body or by applying
pharmacological agents to alter excitability properties.
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