Voltage Dependence of Junctional Conductance in Early Amphibian Embryos

Spray, David C.; Harris, Andrew L.; Bennett, Michael V. L.

doi:10.1126/science.312530

Cited by 185 publications

(93 citation statements)

References 28 publications

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“…S5B). Current flowing via junctions from the pulsed cell C1 into C2 is matched by the first cell, with current of opposite polarity supplied by its voltage clamp to maintain a constant membrane potential (61). Thus, g j between C1 and C2 is calculated from the measured junctional current, I j , that passes through channels at cell junctions between the cell pair divided by the magnitude of the transjunctional voltage, V j (g j = −ΔI j /ΔV j , where ΔV j = V 1f − V 1i and ΔI j = I 2f − I 2i ).…”

Section: Methodsmentioning

confidence: 99%

Matrix-dependent adhesion mediates network responses to physiological stimulation of the osteocyte cell process

Schaffler

Weinbaum

et al. 2013

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

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Osteocytes are bone cells that form cellular networks that sense mechanical loads distributed throughout the bone tissue. Interstitial fluid flow in the lacunar canalicular system produces focal strains at localized attachment sites around the osteocyte cell process. These regions of periodic attachment between the osteocyte cell membrane and its canalicular wall are sites where pN-level fluid-flow induced forces are generated in vivo. In this study, we show that focally applied forces of this magnitude using a newly developed Stokesian fluid stimulus probe initiate rapid and transient intercellular electrical signals in vitro. Our experiments demonstrate both direct gap junction coupling and extracellular purinergic P2 receptor signaling between MLO-Y4 cells in a connected bone cell network. Intercellular signaling was initiated by pN-level forces applied at integrin attachment sites along both appositional and distal unapposed cell processes, but not initiated at their cell bodies with equivalent forces. Electrical coupling was evident in 58% of all cell pairs tested with appositional connections; coupling strength increased with the increasing number of junctional connections. Apyrase, a nucleotidedegrading enzyme, suppressed and abolished force-induced effector responses, indicating a contribution from ATP released by the stimulated cell. This work extends the understanding of how osteocytes modulate their microenvironment in response to mechanical signals and highlights mechanisms of intercellular relay of mechanoresponsive signals in the bone network.cell signaling | electrophysiology | mechanotransduction | junctional conductance I ncreasing evidence indicates that bone homeostasis and osteogenic remodeling require mechanical loading of whole bone tissue (1-4). Interstitial fluid in bone passes through hierarchical levels of porosity when bone tissue is deformed by external loads. The interstitial fluid is the medium that translates endogenous whole tissue mechanical loads to cellular level forces in bone. Measuring the magnitude of endogenous forces acting on osteocytes in vivo has been a major challenge experimentally, but is of significance for investigating force-induced cell signals in vitro. Mathematical models of in vivo forces acting within the bone porosity of the lacunar-canalicular system (LCS) containing osteocytes have theoretically predicted forces between 1 and 10 pN acting on attachment sites along the osteocyte cell process membrane (5-7). These predictions guided the development of a Stokesian fluid stimulus probe (SFSP) used to focally stimulate osteocytes in vitro at in vivo-level forces (8). In this study, we examined the intercellular electrical signals induced by pN-level forces in interconnected MLO-Y4 bone cell networks, and measured the intercellular signaling through gap junction channels and through changes in nonjunctional conductance. Signaling through nonjunctional membranes likely involves ATP release and binding to purinergic receptors (P2Rs), as demonstrated by the partia...

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Section: Methodsmentioning

confidence: 99%

Matrix-dependent adhesion mediates network responses to physiological stimulation of the osteocyte cell process

Schaffler

Weinbaum

et al. 2013

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

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“…On the shortest time scale, it is known that gap-junction channels are gated by voltage and can display multiple voltage-dependent conductance states (Turin and Warner 1977;Spray et al 1979;Neyton and Trautmann 1985;Chen and DeHaan 1992;Bukauskas and Weingart 1993). Voltage-gating is a common property of connexins, although they show substantive differences in their sensitivities.…”

Section: Rapid Regulationmentioning

confidence: 99%

Gap Junctions

Goodenough¹,

Paul²

2009

Cold Spring Harbor Perspectives in Biology

548

440

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“…Furthermore, the direct support for the cell-to-cell channel concept can be observed from measurements of cell-to-cell electrical conductance between paired cells in gap junction. Permeability of the gap junction is demonstrated morphologically and electrophysiologically to be modulated by changes in pH (53,56), intracellular Ca2+ concentration (42,47,48) or membrane potential (26,52).…”

mentioning

confidence: 99%