Modeling and analysis of voltage gating of gap junction channels at a single-channel level.

The advancement of single-channel-level recording via the patch-clamp technique has provided a powerful means of assessing the detailed behaviors of various types of ion channels in native and exogenously expressed cellular environments. However, such recordings of gap junction (GJ) channels are hampered by unique challenges that are related to their unusual intercellular configuration and natural clustering into densely packed plaques. Thus, the methods for reliable cross-correlation of data recorded at macroscopic and single-channel levels are lacking in studies of GJs.

The role of the Cx43/Cx45 gap junction voltage gating on wave propagation and arrhythmogenic activity in cardiac tissue.

Gap junctions (GJs) formed of connexin (Cx) protein are the main conduits of electrical signals in the heart. Studies indicate that the transitional zone of the atrioventricular (AV) node contains heterotypic Cx43/Cx45 GJ channels which are highly sensitive to transjunctional voltage (V). To investigate the putative role of V gating of Cx43/Cx45 channels, we performed electrophysiological recordings in cell cultures and developed a novel mathematical/computational model which, for the first time, combines GJ channel V gating with a model of membrane excitability to simulate a spread of electrical pulses in 2D.

The Amino Terminal Domain and Modulation of Connexin36 Gap Junction Channels by Intracellular Magnesium Ions.

Electrical synapses between neurons in the mammalian CNS are predominantly formed of the connexin36 (Cx36) gap junction (GJ) channel protein. Unique among GJs formed of a number of other members of the Cx gene family, Cx36 GJs possess a high sensitivity to intracellular Mg that can robustly act to modulate the strength of electrical synaptic transmission. Although a putative Mg binding site was previously identified to reside in the aqueous pore in the first extracellular (E1) loop domain, the involvement of the N-terminal (NT) domain in the atypical response of Cx36 GJs to pH was shown to depend on intracellular levels of Mg.

Four-State Model for Simulating Kinetic and Steady-State Voltage-Dependent Gating of Gap Junctions.

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, V, the voltage difference between two coupled cells. Voltage gating of GJs could play a physiological role, particularly in excitable cells, which can generate large transients in membrane potential during the propagation of action potentials.

Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH) and cytosolic magnesium ion concentration ([Mg]), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail.

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

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.

Stochastic Model of Gap Junctions Exhibiting Rectification and Multiple Closed States of Slow Gates.

Gap-junction (GJ) channels formed from connexin (Cx) proteins provide direct pathways for electrical and metabolic cell-cell communication. Earlier, we developed a stochastic 16-state model (S16SM) of voltage gating of the GJ channel containing two pairs of fast and slow gates, each operating between open (o) and closed (c) states. However, experimental data suggest that gates may in fact contain two or more closed states.