Reverberation of excitation in neuronal networks interconnected through voltage-gated gap junction channels

Maciunas, Kestutis; Šnipas, Mindaugas; Paulauskas, Nerijus; Bukauskas, Feliksas F.

doi:10.1085/jgp.201511488

Cited by 16 publications

(18 citation statements)

References 84 publications

(184 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…R in of the presynaptic cell was close to 125 MΩ, which is within the range of experimentally measured values in MesV neurons [ 30 ]. Gating parameters of a 36SM were chosen to resemble Cx36 [ 19 , 20 ], a major connexin forming electrical synapses between neurons in the central nervous system.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating

et al. 2017

Self Cite

View full text Add to dashboard Cite

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 accounts for direction-dependent asymmetry, as well as for short- and long-term plasticity of electrical synapses. Our modeling results demonstrate that such complex behavior of the electrical synapse is important in shaping the response of coupled neurons.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Earlier [ 20 ], we combined a 16SM of gap junction channel gating and rectification with the Hodgkin–Huxley (HH) equations [ 21 ]. The developed model (HH-16SM) allowed us to evaluate the kinetics of junctional conductance during the spread of excitation in neuronal networks.…”

Section: Introductionmentioning

confidence: 99%

Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rectification of unitary conductance was evaluated using the same method as originally proposed in [8], and later applied in our modelling studies [13,18]. That is, we presumed that the unitary conductance (γ) of an open or a closed hemichannel is a function of voltage (V) according to:…”

Section: Rectification Of Unitary Conductancementioning

confidence: 99%

4-state model for simulating kinetic and steady-state voltagedependent gating of gap junctions

Šnipas

Kraujalis

Maciunas

et al. 2019

Preprint

View full text Add to dashboard Cite

Gap junction (GJ) channels, formed of connexin (Cx) proteins, provide a direct pathway for metabolic and electrical cell-to-cell communication. These specialized channels are not just passive conduits for the passage of ions and metabolites, but have been shown to gate robustly in response to transjunctional voltage, Vj, the voltage difference between two coupled cells and are regulated by various chemical factors. Voltage gating of GJs may play a physiological role, particularly in excitable cells which can exhibit large transients in membrane potential during the generation of an action potential. We present a mathematical/computational model of GJ channel voltage gating to assess properties of GJ channels that takes into account contingent gating of two series hemichannels and the distribution of Vj across each hemichannel. From electrophysiological recordings in cell cultures transfected with Cx43 and Cx45, isoforms that are expressed in cardiac tissue, data sets were fit simultaneously using global optimization. The results showed that the model is capable of describing both steady-state and kinetic properties of homotypic and heterotypic GJ channels composed of these connexins. Moreover, mathematical analyses showed that the model can be simplified to a reversible two-state system and solved analytically, using a rapid equilibrium assumption. Given that excitable cells are arranged in interconnected networks, the equilibrium assumption allows for a substantial reduction in computation time, which is useful in simulations of large clusters of coupled cells. Overall, this model can serve not just as a modeling tool, but also to provide a means of testing GJ channel gating behavior. SignificanceGap junction (GJ) channels gate in response to transjunctional voltage which provides the capacity for dynamic regulation of intercellular coupling. Kinetic properties of GJs in modeling studies have been infrequently addressed and we present a computational model of voltage gating that can account for both kinetic and steady-state changes in junctional conductance, gj. Although GJs possess two gating mechanisms, our analysis indicates that changes in gj for each voltage polarity can be adequately described by a kinetic scheme describing a single mechanism in each of the hemichannels, suggesting functional dominance of one mechanism over a substantial voltage range. This property allowed for model simplification that can be applied for efficient simulation of sizeable cell clusters and analyses of electrophysiological data.

show abstract

“…Because they determine a cell's resting potential (by allowing electrical inputs from neighboring cells) but are themselves voltage-gated, they implement positive feedback loops that are an ideal mechanism for stabilizing physiological signals as stable memories ( Levin, 2014b ; Palacios-Prado and Bukauskas, 2009 ). It is thus no accident that brains capitalize extensively on gap junction-mediated plasticity for learning and memory in the CNS ( Allen et al, 2011 ; Maciunas et al, 2016 ; Wang and Belousov, 2011 ; Wu et al, 2011 ).…”

Section: Which Memories Might Survive Fission?mentioning

confidence: 99%

Vertically- and horizontally-transmitted memories – the fading boundaries between regeneration and inheritance in planaria

2016

View full text Add to dashboard Cite

The Weismann barrier postulates that genetic information passes only from the germline to the soma and not in reverse, thus providing an obstacle to the inheritance of acquired traits. Certain organisms such as planaria – flatworms that can reproduce through asymmetric fission – avoid the limitations of this barrier, thus blurring the distinction between the processes of inheritance and development. In this paper, we re-evaluate canonical ideas about the interaction between developmental, genetic and evolutionary processes through the lens of planaria. Biased distribution of epigenetic effects in asymmetrically produced parts of a regenerating organism could increase variation and therefore affect the species' evolution. The maintenance and fixing of somatic experiences, encoded via stable biochemical or physiological states, may contribute to evolutionary processes in the absence of classically defined generations. We discuss different mechanisms that could induce asymmetry between the two organisms that eventually develop from the regenerating parts, including one particularly fascinating source – the potential capacity of the brain to produce long-lasting epigenetic changes.

show abstract

Reverberation of excitation in neuronal networks interconnected through voltage-gated gap junction channels

Abstract: Voltage-dependent gap junction gating contributes to reverberation in neuronal circuits.

Cited by 16 publications

References 84 publications

Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating

Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating

4-state model for simulating kinetic and steady-state voltagedependent gating of gap junctions

Vertically- and horizontally-transmitted memories – the fading boundaries between regeneration and inheritance in planaria

Contact Info

Product

Resources

About