Electrical Cell Coupling in Rabbit Sino Atrial Node and Atrium Experimental and Theoretical Evaluation

Bukauskas, Feliksas F.; Gutman, Aron M.; Kišūnas, Klemensas; Veteikis, Romualdas

doi:10.1007/978-94-009-7535-4_11

Cited by 12 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Connexin-based GJ channels and hemichannels may serve as conduits for intracellular acid dissipation, especially because the classical sarcolemmal routes for acid efflux appear to be inhibited (44). Studies of normal/ischemia border regions in isolated preparations of the heart showed that preservation of ischemic cells by neighboring cells exposed to normal perfusion is greater in the longitudinal than in transverse direction of the fibers, consistent with ∼7-to 10-fold stronger cell-cell coupling in the longitudinal direction (45). However, under severe ischemic conditions GJ communication is blocked (46), and this blockage may limit both the spread of damage and the cell-rescuing/ preservation effect of GJs.…”

Section: Discussionmentioning

confidence: 93%

pH-dependent modulation of voltage gating in connexin45 homotypic and connexin45/connexin43 heterotypic gap junctions

Palacios-Prado

Briggs

Skeberdis

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Intracellular pH (pH i ) can change during physiological and pathological conditions causing significant changes of electrical and metabolic cell-cell communication through gap junction (GJ) channels. In HeLa cells expressing wild-type connexin45 (Cx45) as well as Cx45 and Cx43 tagged with EGFP, we examined how pH i affects junctional conductance (g j ) and g j dependence on transjunctional voltage (V j ). To characterize V j gating, we fit the g j -V j relation using a stochastic four-state model containing one V j -sensitive gate in each apposed hemichannel (aHC); aHC open probability was a Boltzmann function of the fraction of V j across it. Using the model, we estimated gating parameters characterizing sensitivity to V j and number of functional channels. In homotypic Cx45 and heterotypic Cx45/Cx43-EGFP GJs, pH i changes from 7.2 to ∼8.0 shifted g j -V j dependence of Cx45 aHCs along the V j axis resulting in increased probability of GJ channels being in the fully open state without change in the slope of g j dependence on V j . In contrast, acidification shifted g j -V j dependence in the opposite direction, reducing open probability; acidification also reduced the number of functional channels. Correlation between the number of channels in Cx45-EGFP GJs and maximal g j achieved under alkaline conditions showed that only ∼4% of channels were functional. The acid dissociation constant (pK a ) of g j -pH i dependence of Cx45/Cx45 GJs was ∼7. The pK a of heterotypic Cx45/Cx43-EGFP GJs was lower, ∼6.7, between the pK a s of Cx45 and Cx43-EGFP (∼6.5) homotypic GJs. In summary, pH i significantly modulates junctional conductance of Cx45 by affecting both V j gating and number of functional channels.cell-cell coupling | pH-dependent gating | EGFP | hemichannel | connexon C hanges in intracellular pH (pH i ) take place under different physiological and pathological conditions, and H + ions have a broad effect on cell function including cell-cell electrical and metabolic communication mediated by gap junctions (GJs) and paracrine signaling through nonjunctional/unapposed hemichannels (1-4). Modest pH i changes have been observed under normal physiological conditions [e.g., changes of neuronal activity or the resting potential (5, 6)], and greater changes occur under pathological conditions such as hypoxia, ischemia, or epilepsy (4,7,8).During the last decade, significant progress has been made toward understanding the molecular mechanisms of pH-dependent modulation of GJs and hemichannels (2, 9-12). Several domains in the cytoplasmic loop and C terminus of connexin43 (Cx43) appear to be involved in pH-dependent gating (2, 9, 11, 12). Furthermore, pH-dependent interaction of connexins with other cytoplasmic proteins may be important in the remodeling of connexins and in protection from lesion spread after local ischemic injury (13,14).GJs provide channels with an inner diameter of ∼1.4 nm between the interiors of the coupled cells. This link allows the spread of electrical potential and small metabolites. Each GJ cha...

show abstract

Section: Discussionmentioning

confidence: 93%

pH-dependent modulation of voltage gating in connexin45 homotypic and connexin45/connexin43 heterotypic gap junctions

Palacios-Prado

Briggs

Skeberdis

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The optic nerve diameter in Nectwus is smaller than the length constant of its glial syncytium indicating that this system is restricted in two dimensions; this could contribute to its relatively large length constant, which is comparable to the length constant of uncoupled oligodendrocytes (Kettenmann, 1987b). It can be assumed that enlarging a syncytium from two to three dimensions will decrease the length constant (Bukauskas et al, 1982). Our data from a twodimensional network of astrocytes, therefore, suggest that the length constant of a three-dimensional astrocytic syncytium, as in the intact brain, would tend to be smaller than 100 pm; given the many differences between the in vivo and in vitro situations, the length constant estimates of about 200 and 50 pM for the glial networks in rat and frog brains, respectively (Gardner-Medwin, 1985;Gardner-Medwin and Nicholson, 19831, are in the appropriate range.…”

Section: The Length Constant Of the Astrocytic Syneytiummentioning

confidence: 99%

Electrical coupling between astrocytes and between oligodendrocytes studied in mammalian cell cultures

Kettenmann

Ransom

1988

Glia

166

114

View full text Add to dashboard Cite

The characteristics of electrical coupling between astrocytes and between oligodendrocytes were analyzed in cell cultures derived from rodent central nervous system. Experiments were carried out by impaling one member of a glial pair with separate voltage recording and current passing electrodes (cell 1) and the other cell, a measured distance from the first, with a voltage-recording electrode (cell 2). Astrocyte pairs within 300 microns of one another were always coupled. The coupling ratio was determined for 23 astrocytic pairs various distances apart, and decreased with distance in a roughly exponential manner. The average coupling ratio of astrocytes within 100 microns of each other was 0.44 +/- 0.32. Oligodendrocytes were less strongly coupled to each other than astrocytes. Even cells immediately adjacent to one another were often uncoupled. Among coupled oligodendrocytes within 100 microns of each other, the average coupling ratio was 0.11 +/- 0.1. Current passage between pairs of astrocytes and pairs of oligodendrocytes was nonrectifying. Application of 0.5 mM BaCl2 or 44.6 mM CsCl (substituted for NaCl) depolarized and increased the input resistance of astrocytes and oligodendrocytes. These ions also increased the coupling ratio in astrocyte pairs and oligodendrocyte pairs; this effect was rapid in onset and completely reversible. Ba++ and Cs+ appear to block resting K+ conductance in glia and probably increase the coupling ratio by increasing the effective length constant of the glial membrane without any direct effect on junctional resistance. In three cases, oligodendrocyte pairs that appear uncoupled in normal solution exhibited coupling in the presence of BaCl2 or CsCl. This suggests that oligodendrocytes may be widely coupled by junctions that provide only weak electrical interaction; such junctions might be important for the exchange of small metabolically active molecules. The strong electrical coupling among astrocytes, in concert with their K+-selective membrane conductance, would provide for an electrical syncytium well designed to transport K+ away from areas of focal extracellular accumulation (i.e., the spatial buffer mechanism), and these cells, more than oligodendrocytes, may provide this function.

show abstract

“…Second, we varied the radial distribution of intercellular resistivity. We assumed a value of 600 Q cm (Bukauskas et al, 1982) as our "normal" value and investigated the effects of radial variation in this resistivity. Our results with two coupled cells showed that the coupling resistance affected both the ability of the SA cell to pace and its ability to drive the atrial cell.…”

Section: Biophysical Journal Volume 50 1986mentioning

confidence: 99%

Propagation through electrically coupled cells. How a small SA node drives a large atrium

Joyner¹,

Capelle²

1986

Biophysical Journal

239

167

View full text Add to dashboard Cite

Each normal cardiac cycle is started by an action potential that is initiated in the sino-atrial (SA) node by automaticity of the SA nodal cells. This action potential then propagates from the SA node into the surrounding atrial cells. We have done numerical simulations of electrically coupled cells to understand how a small SA node can be spontaneously active and yet be sufficiently electrically coupled to the surrounding quiescent atrial cells to initiate an action potential in the atrial cells. Our results with a simple model of two coupled cells and a more complex model of a two-dimensional sheet of cells suggest that some degree of electrical uncoupling of the cells within the SA node may be an essential design feature of the normal SA-atrial system.

show abstract

Electrical Cell Coupling in Rabbit Sino Atrial Node and Atrium Experimental and Theoretical Evaluation

Cited by 12 publications

References 20 publications

pH-dependent modulation of voltage gating in connexin45 homotypic and connexin45/connexin43 heterotypic gap junctions

pH-dependent modulation of voltage gating in connexin45 homotypic and connexin45/connexin43 heterotypic gap junctions

Electrical coupling between astrocytes and between oligodendrocytes studied in mammalian cell cultures

Propagation through electrically coupled cells. How a small SA node drives a large atrium

Contact Info

Product

Resources

About