Propagation malfunctions due to gap junction dysregulation
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Data publicació2015-01-02
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Abstract
Gap junctions are membrane channels that connect the
cytoplasm of adjacent cells allowing the cell-to-cell elec-
trical coupling necessary for action potential propagation.
Pathological conditions, such as malformations in connex-
ins, mutations affecting phosphorylation of regulatory sites
of connexins, alterations in gap junction organization, and
type and quantity of connexin expression, can impede the
normal electrical propagation. All these malfunctions can
produce a dispersion of repolarization, implicated in ven-
tricular arrhythmias. In fact, ventricular tachycardia and
spontaneous ventricular arrhythmia occurred in more than
twice as many connexin deficient hearts than wild-type
hearts.
We perform numerical simulations of a human ventric-
ular model in order to mimic some of these pathological
conditions. In particular, we consider a diminished Cx43
connexin expression, as well as altered connexin conduc-
tance dynamics, i.e., modified maximum and minimum
conductances gmax and gmin, half-inactivation voltage
V1/2 and decay kinetics. Physiologically these modifica-
tions can appear due to mutations or to different connexin
configurations, i.e., forming heteromeric channels. Under
these conditions we study the change in action potential
duration (APD) and CV-restitution properties. We observe
that, although CV diminishes with decreased connexin ex-
pression, the APD remains almost constant up to the point
of conduction block. Also, propagation differs for constant
or time-dependent voltage conductance, conduction block
occurring earlier for the former. While mutations result-
ing in a stronger dependence of the delay time produced
an appreciable change intercellular conductances, this ef-
fect was not so important when the mutations affected the
overall delay time. Thus, our results suggest that a correct
description of gap junctional conductance is of big impor-
tance for understanding action potential propagation un-
der pathological conditions.
CitacióRodriguez Cantalapiedra, I., Peñaranda, A., Echebarria, B. Propagation malfunctions due to gap junction dysregulation. "Computing in Cardiology", 2 Gener 2015, vol. 41, p. 1045-1048.
ISSN2325-8861
Versió de l'editorhttp://www.cinc.org/archives/2014/pdf/1045.pdf
Col·leccions
- GICITED - Grup Interdiciplinari de Ciència i Tecnologia en l'Edificació - Articles de revista [190]
- Departament de Física - Articles de revista [2.209]
- BIOCOM-SC - Biologia Computacional i Sistemes Complexos - Articles de revista [226]
- ANCORA - Anàlisi i control del ritme cardíac - Articles de revista [24]
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