Title Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating /
Authors Snipas, Mindaugas ; Rimkute, Lina ; Kraujalis, Tadas ; Maciunas, Kestutis ; Bukauskas, Feliksas F
DOI 10.1371/journal.pcbi.1005464
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Is Part of PLoS computational biology.. San Francisco : Public library of science. 2017, vol. 13, iss. 4, art. no. e1005464, p. 1-26.. ISSN 1553-734X. eISSN 1553-7358
Keywords [eng] connexin 45 ; gap junction protein ; magnesium
Abstract [eng] We combined the Hodgkin–Huxley equations and a 36-state model of gap junction channel gating to simulate electrical signal transfer through electrical synapses. Differently from most previous studies, our model can account for dynamic modulation of junctional conductance during the spread of electrical signal between coupled neurons. The model of electrical synapse is based on electrical properties of the gap junction channel encompassing two fast and two slow gates triggered by the transjunctional voltage. We quantified the influence of a difference in input resistances of electrically coupled neurons and instantaneous conductance–voltage rectification of gap junctions on an asymmetry of cell-to-cell signaling. We demonstrated that such asymmetry strongly depends on junctional conductance and can lead to the unidirectional transfer of action potentials. The simulation results also revealed that voltage spikes, which develop between neighboring cells during the spread of action potentials, can induce a rapid decay of junctional conductance, thus demonstrating spiking activity-dependent short-term plasticity of electrical synapses. This conclusion was supported by experimental data obtained in HeLa cells transfected with connexin45, which is among connexin isoforms expressed in neurons. Moreover, the model allowed us to replicate the kinetics of junctional conductance under different levels of intracellular concentration of free magnesium ([Mg2+]i), which was experimentally recorded in cells expressing connexin36, a major neuronal connexin. We demonstrated that such [Mg2+]i-dependent long-term plasticity of the electrical synapse can be adequately reproduced through the changes of slow gate parameters of the 36-state model. This suggests that some types of chemical modulation of gap junctions can be executed through the underlying mechanisms of voltage gating. Overall, the developed model acco.
Published San Francisco : Public library of science
Type Journal article
Language English
Publication date 2017