Loss and reappearance of gap junctions in regenerating liver

Changes in intercellular junctional morphology associated with rat liver regeneration were examined in a freeze-fracture study. After a two-thirds partial hepatectomy, both gap junctions and zonulae occludentes were drastically altered. Between 0 and 20 h after partial hepatectomy, the junctions appeared virtually unchanged. 28 h after partial hepatectomy, however, the large gap junctions usually located close to the bile canaliculi and the small gap junctions enmeshed within the strands of the zonulae occudentes completely disappeared. Although the zonulae occludentes bordering the bile canaliculi apparently remained intact, numerous strands could now be found oriented perpendicular to the canaliculi. In some instances, the membrane outside the canaliculi was extensively filled with isolated junctional strands, often forming very complex configurations. About 40 h after partial hepatectomy, very many small gap junctions reappeared in close association with the zonulae occludentes. Subsequently, gap junctions increased in size and decreased in number until about 48 h after partial hepatectomy when gap junctions were indistinguishable in size and number from those of control animals. The zonulae occludentes were again predominantly located around the canalicular margins. These studies provide further evidence for the growth of gap junctions by the accretion of particles and of small gap junctions to form large maculae

Comparative Analysis of the Major Polypeptides from Liver Gap Junctions and Lens Fiber Junctions

Gap junctions from rat liver and fiber junctions from bovine lens have similar septilaminar profiles when examined by thin-section electron microscopy and differ only slightly with respect to the packing of intramembrane particles in freeze-fracture images. These similarities have often led to lens fiber junctions being referred to as gap junctions. Junctions from both sources were isolated as enriched subcellular fractions and their major polypeptide components compared biochemically and immunochemically. The major liver gap junction polypeptide has an apparent molecular weight of 27,000, while a 25,000-dalton polypeptide is the major component of lens fiber junctions. The two polypeptides are not homologous when compared by partial peptide mapping in SDS. In addition, there is not detectable antigenic similarity between the two polypeptides by immunochemical criteria using antibodies to the 25,000-dalton lens fiber junction polypeptide. Thus, in spite of the ultrastructural similarities, the gap junction and the lens fiber junction are comprised of distinctly different polypeptides, suggesting that the lens fiber junction contains a unique gene product and potentially different physiological properties

Molecular basis of gap junctional communication in the CNS of the leech Hirudo medicinalis

Gap junctions are intercellular channels that allow the passage of ions and small molecules between cells. In the nervous system, gap junctions mediate electrical coupling between neurons. Despite sharing a common topology and similar physiology, two unrelated gap junction protein families exist in the animal kingdom. Vertebrate gap junctions are formed by members of the connexin family, whereas invertebrate gap junctions are composed of innexin proteins. Here we report the cloning of two innexins from the leech Hirudo medicinalis. These innexins show a differential expression in the leech CNS: Hm-inx1 is expressed by every neuron in the CNS but not in glia, whereas Hm-inx2 is expressed in glia but not neurons. Heterologous expression in the paired Xenopus oocyte system demonstrated that both innexins are able to form functional homotypic gap junctions. Hm-inx1 forms channels that are not strongly gated. In contrast, Hm-inx2 forms channels that are highly voltage-dependent; these channels demonstrate properties resembling those of a double rectifier. In addition, Hm-inx1 and Hm-inx2 are able to cooperate to form heterotypic gap junctions in Xenopus oocytes. The behavior of these channels is primarily that predicted from the properties of the constituent hemichannels but also demonstrates evidence of an interaction between the two. This work represents the first demonstration of a functional gap junction protein from a Lophotrochozoan animal and supports the hypothesis that connexin-based communication is restricted to the deuterostome clade

Connexin36 knockout mice display increased sensitivity to pentylenetetrazol-induced seizure-like behaviors

Large-scale synchronous firing of neurons during seizures is modulated by electrotonic coupling between neurons via gap junctions. To explore roles for connexin36 (Cx36) gap junctions in seizures, we examined the seizure threshold of connexin36 knockout (Cx36KO) mice using a pentylenetetrazol (PTZ) model

Multiple energy gap features of superconducting FeSe investigated by tunneling spectroscopy

Planar tunneling junctions of the presumably unconventional superconductor FeSe were prepared and investigated. The junctions consisted of FeSe/AlOx/Ag multilayers patterned lithographically into mesa structures. Bias voltage dependent differential conductivities dI/dV(V) of junctions in the tunneling, intermediate barrier strength, and metallic regimes were investigated. Depending on the barrier type between two and four features of the conductivity were obtained, which are discussed in the framework of multiple superconducting energy gaps. Specifically we reproduced with all barrier types an established energy gap and discovered an additional large gap structure. From two further conductivity features presumable one originates from another superconducting gap and the other from resonant states.Comment: 5 pages, 5 figure

Learning theories reveal loss of pancreatic electrical connectivity in diabetes as an adaptive response

Cells of almost all solid tissues are connected with gap junctions which permit the direct transfer of ions and small molecules, integral to regulating coordinated function in the tissue. The pancreatic islets of Langerhans are responsible for secreting the hormone insulin in response to glucose stimulation. Gap junctions are the only electrical contacts between the beta-cells in the tissue of these excitable islets. It is generally believed that they are responsible for synchrony of the membrane voltage oscillations among beta-cells, and thereby pulsatility of insulin secretion. Most attempts to understand connectivity in islets are often interpreted, bottom-up, in terms of measurements of gap junctional conductance. This does not, however explain systematic changes, such as a diminished junctional conductance in type 2 diabetes. We attempt to address this deficit via the model presented here, which is a learning theory of gap junctional adaptation derived with analogy to neural systems. Here, gap junctions are modelled as bonds in a beta-cell network, that are altered according to homeostatic rules of plasticity. Our analysis reveals that it is nearly impossible to view gap junctions as homogeneous across a tissue. A modified view that accommodates heterogeneity of junction strengths in the islet can explain why, for example, a loss of gap junction conductance in diabetes is necessary for an increase in plasma insulin levels following hyperglycemia.Comment: 15 pages, 5 figures. To appear in PLoS One (2013

Large tunable image-charge effects in single-molecule junctions

The characteristics of molecular electronic devices are critically determined by metal-organic interfaces, which influence the arrangement of the orbital levels that participate in charge transport. Studies on self-assembled monolayers (SAMs) show (molecule-dependent) level shifts as well as transport-gap renormalization, suggesting that polarization effects in the metal substrate play a key role in the level alignment with respect to the metal's Fermi energy. Here, we provide direct evidence for an electrode-induced gap renormalization in single-molecule junctions. We study charge transport in single porphyrin-type molecules using electrically gateable break junctions. In this set-up, the position of the occupied and unoccupied levels can be followed in situ and with simultaneous mechanical control. When increasing the electrode separation, we observe a substantial increase in the transport gap with level shifts as high as several hundreds of meV for displacements of a few \aa ngstroms. Analysis of this large and tunable gap renormalization with image-charge calculations based on atomic charges obtained from density functional theory confirms and clarifies the dominant role of image-charge effects in single-molecule junctions

Gap junctions and emergent rhythms

Gap junction coupling is ubiquitous in the brain, particularly between the dendritic trees of inhibitory interneurons. Such direct non-synaptic interaction allows for direct electrical communication between cells. Unlike spike-time driven synaptic neural network models, which are event based, any model with gap junctions must necessarily involve a single neuron model that can represent the shape of an action potential. Indeed, not only do neurons communicating via gaps feel super-threshold spikes, but they also experience, and respond to, sub-threshold voltage signals. In this chapter we show that the so-called absolute integrate-and-fire model is ideally suited to such studies. At the single neuron level voltage traces for the model may be obtained in closed form, and are shown to mimic those of fast-spiking inhibitory neurons. Interestingly in the presence of a slow spike adaptation current the model is shown to support periodic bursting oscillations. For both tonic and bursting modes the phase response curve can be calculated in closed form. At the network level we focus on global gap junction coupling and show how to analyze the asynchronous firing state in large networks. Importantly, we are able to determine the emergence of non-trivial network rhythms due to strong coupling instabilities. To illustrate the use of our theoretical techniques (particularly the phase-density formalism used to determine stability) we focus on a spike adaptation induced transition from asynchronous tonic activity to synchronous bursting in a gap-junction coupled network