Emergent properties of electrically coupled smooth muscle cells

Asynchronous and synchronous calcium oscillations occur in a variety of cells. A well-established pathway for intercellular communication is provided by gap junctions which connect adjacent cells and can mediate electrical and chemical coupling. Several experimental studies report that cells presenting only a transient increase when freshly dispersed may oscillate when they are coupled. Such observations suggest that the role of gap junctions is not only to coordinate calcium oscillations of adjacent cells. Gap junctions may also be important to generate oscillations. Here we illustrate the emergent properties of electrically coupled smooth muscle cells using a model that we recently proposed. A bifurcation analysis in the case of two cells reveals that synchronous and asynchronous calcium oscillations can be induced by electrical coupling. In a larger population of smooth muscle cells, electrical coupling may result in the creation of groups of cells presenting synchronous calcium oscillations. The elements of one group may be distant from each other. Moreover, our results highlight a general mechanism by which gap junctional electrical coupling can give rise to out of phase calcium oscillations in smooth muscle cells that are non-oscillating when uncoupled. All these observations remain true in the case of non-identical cells, except that the solution corresponding to synchronous calcium oscillations disappears and that the formation of groups is sensitive to the degree of heterogeneit

M-Theory on S^1/Z_2 : New Facts from a Careful Analysis

We carefully re-examine the issues of solving the modified Bianchi identity, anomaly cancellations and flux quantization in the S^1/Z_2 orbifold of M-theory using the boundary-free "upstairs" formalism, avoiding several misconceptions present in earlier literature. While the solution for the four-form G to the modified Bianchi identity appears to depend on an arbitrary parameter b, we show that requiring G to be globally well-defined, i.e. invariant under small and large gauge and local Lorentz transformations, fixes b=1. This value also is necessary for a consistent reduction to the heterotic string in the small-radius limit. Insisting on properly defining all fields on the circle, we find that there is a previously unnoticed additional contribution to the anomaly inflow from the eleven-dimensional topological term. Anomaly cancellation then requires a quadratic relation between b and the combination lambda^6/kappa^4 of the gauge and gravitational coupling constants lambda and kappa. This contrasts with previous beliefs that anomaly cancellation would give a cubic equation for b. We observe that our solution for G automatically satisfies integer or half-integer flux quantization for the appropriate cycles. We explicitly write out the anomaly cancelling terms of the heterotic string as inherited from the M-theory approach. They differ from the usual ones by the addition of a well-defined local counterterm. We also show how five-branes enter our analysis.Comment: 32 pages, version to appear in Nucl. Phys. B, no figures, uses PHYZZ

Force transmission in migrating cells

Analysis of the relationship between actin network velocity and traction forces at the substrate shows that force transmission mechanisms vary with distinct regions of the cell

Evidence for signaling via gap junctions from smooth muscle to endothelial cells in rat mesenteric arteries: possible implication of a second messenger

We investigated heterocellular communication in rat mesenteric arterial strips at the cellular level using confocal microscopy. To visualize Ca(2+) changes in different cell populations, smooth muscle cells (SMCs) were loaded with Fluo-4 and endothelial cells (ECs) with Fura red. SMC contraction was stimulated using high K(+) solution and Phenylephrine. Depending on vasoconstrictor concentration, intracellular Ca(2+) concentration ([Ca(2+)](i)) increased in a subpopulation of ECs 5-11s after a [Ca(2+)](i) rise was observed in adjacent SMCs. This time interval suggests chemical coupling between SMCs and ECs via gap junctions. As potential chemical mediators we investigated Ca(2+) or inositol 1,4,5-trisphosphate (IP(3)). First, phospholipase C inhibitor U-73122 was added to prevent IP(3) production in response to the [Ca(2+)](i) increase in SMCs. In high K(+) solution, all SMCs presented global and synchronous [Ca(2+)](i) increase, but no [Ca(2+)](i) variations were detected in ECs. Second, 2-aminoethoxydiphenylborate, an inhibitor of IP(3)-induced Ca(2+) release, reduced the number of flashing ECs by 75+/-3% (n = 6). The number of flashing ECs was similarly reduced by adding the gap junction uncoupler palmitoleic acid. Thus, our results suggest a heterocellular communication through gap junctions from SMCs to ECs by diffusion, probably of IP(3)