Cell-to-cell communication in the heart: structure-function correlations

Summary The communicating cell junctions that ensure the electrical and diffusional continuity of the intracellular space in the heart fibres can be switched from their normal conducting, or opened state, to an exceptional non-conducting or closed state. This electrical uncoupling is observed after cell injury in the presence of Ca²⁺ ions in the extracellular fluid, after metabolic inhibition and in the presence of aliphatic alcohols (C₆ to C₉). The correlations between electrical uncoupling and gap junction morphology in the heart are briefly reviewed. A decrease of the distance between P-face particles and between the E-face pits has been found in all investigations^{3,10,16,18,55}, but the functional significance of this observation is not understood at present. A quantitatively very similar decrease of the average particle diameter (about –0.7 nm) has been measured in glutaraldehyde-fixed sheep Purkinje fibres¹⁶ and in unfixed, quickly frozen rat auricles¹⁸ that had been electrically uncoupled by three different procedures. About half of this decrease was reversible on short-term electrical recoupling (within 20 min). It is concluded that a measurable decrease of the connexon diameter correlates with electrical uncoupling.     

Sodium pump: Its importance to intercellular communication in heart fibres

Summary The effect of ouabain on the electrical coupling of canine Purkinje cells was investigated. It was found that the glycoside decreases cell communication through an increase in junctional resistance, what supports the view² that the sodium pump has an important role on the control of cell communication.This work was supported by Grant No. HL-10897 from the National Heart and Lung Institute, Bethesda, Maryland; from the P.R. Heart Association and from the General Research Support Grant.     

Sodium pump: its importance to intercellular communication in heart fibres.

The effect of ouabain on the electrical coupling of canine Purkinje cells was investigated. It was found that the glycoside decreases cell communication through an increase in junctional resistance, what supports the view that the sodium pump has an important role on the control of cell communication.     

Cell-to-cell coupling studied in isolated ventricular cell pairs

Summary Cell pairs isolated from adult rat and guinea pig ventricles were used to study the electrical properties of the nexal membrane. Each cell of a pair was connected to a voltage-clamp system so as to enable whole-cell, tight-seal recording. The current-voltage relationship of the nexal membrane was found to be linear, revealing a resistance r_n of 2–4 M. r_n was insensitive to the sarcolemmal membrane potential (range:–90 to +30 mV), and exerted no time-dependent gating behavior (range: 0.1 to 10 s). Lowering pH_i yielded a small increase in r_n. Vigorous elevations in [Ca²⁺]_i gave rise to an increase in r_n which was associated with a cell shortening. Uncoupling caused by aliphatic alcohols or halothane did not produce cell shortening. Cell pairs were also used to study action potential transfer.     

Cell-to-cell coupling studied in isolated ventricular cell pairs

Cell pairs isolated from adult rat and guinea pig ventricles were used to study the electrical properties of the nexal membrane. Each cell of a pair was connected to a voltage-clamp system so as to enable whole-cell, tight-seal recording. The current-voltage relationship of the nexal membrane was found to be linear, revealing a resistance rn of 2-4 M omega. rn was insensitive to the sarcolemmal membrane potential (range: -90 to +30 mV), and exerted no time-dependent gating behavior (range: 0.1 to 10 s). Lowering pHi yielded a small increase in rn. Vigorous elevations in [Ca2+]i gave rise to an increase in rn which was associated with a cell shortening. Uncoupling caused by aliphatic alcohols or halothane did not produce cell shortening. Cell pairs were also used to study action potential transfer.     

Cell-to-cell coupling studied by diffusional methods in myocardial cells

The diffusion of large molecular substances from cell to cell in multicellular and enzymatically isolated cell pairs is described. Permeability of the gap junctional membrane to these molecules and the critical diffusing diameter of the myocardial gap junctional channel are discussed.     

Cell-to-cell transmission in the activation of in situ nematocytes in acontia ofCalliactis parasitica

Summary It is reported that Ca²⁺-induced discharge of in situ nematocytes of acontia ofCalliactis parasitica can occur by cell-to-cell transmission along the acontial filament at a speed that averages 9.8·10^–3 cm^–1. The discharge is preceded by protrusion of nematocytes that proceeds along the acontium at a slightly higher speed.     

Cell-to-cell coupling studied by diffusional methods in myocardial cells

Summary The diffusion of large molecular substances from cell to cell in multicellular and enzymatically isolated cell pairs is described. Permeability of the gap junctional membrane to these molecules and the critical diffusing diameter of the myocardial gap junctional channel are discussed.     

Heparan sulfate-protein interactions: therapeutic potential through structure-function insights

Heparin and the related glycosaminoglycan, heparan sulfate, bind a myriad of proteins. The structural diversity of heparin and heparan sulfates is enormous, but differences in the conformational flexibility of the monosaccharide constituents add extra complexity and may influence protein binding. Silencing genes for heparin/ heparan sulfate biosynthetic enzymes profoundly affects mammalian development. Thus, altering the structure of heparan sulfate chains can alter protein binding and embryo development. Different heparan sulfate structures are located in particular tissue sites, and these structures are recognised by different sets of proteins. Regulation of certain heparan sulfate-protein interactions by pH or cations is described. Heparin/heparan sulfate structures are viewed as potential therapeutics for a variety of diseases. An understanding at the molecular and functional levels of the specificity and affinity of heparan sulfate-protein interactions is crucial for designing heparin-inspired drugs. How the development of synthesis techniques is facilitating structure-function analyses and drug development is discussed.Received 6 July 2004; received after revision 16 September 2004; accepted 28 September 2004     

Clostridial neurotoxins: structure-function led design of new therapeutics

The neurotoxins produced by various species of Clostridia are the causative agents of botulism and tetanus. The ability of the toxins, specifically those of the botulinum neurotoxin family, to disrupt neurotransmission has been exploited for use in several medical indications and now represents the therapeutic option of choice in a number of cases. Clostridial neurotoxins have been discovered to have a multi-domain structure that is shared between the various proteins of the family, and it has also been determined that each domain contributes a specific role to the holotoxin. The extensive use of recombinant expression approaches, along with solution of multiple crystallographic structures of individual domains, has enabled researchers to explore structurefunction relationships of the toxin domains more closely. These advances have facilitated a greater understanding of the potential use of individual domains for a wide variety of purposes, including the development of new therapeutics. Received 21 October 2005; received after revision 10 November 2005; accepted 16 November 2005     

Sex pheromone communication in the lepidoptera: New research progress

Summary Significant progress has been made recently in research on lepidopterous sex pheromones. Advances in understanding the biochemical, neurobiological, and behavioral events that results in both successful and unsuccessful pheromone communication have allowed researchers to gain new insights into the genetic control and evolution of phermone systems.     

Stereoselectivity in mammalian chemical communication: Male mouse pheromones

Two male mouse pheromones, 3,4-dehydro-exo-brevicomin (DHB) and 2-sec-butyldihydrothiazole (SBT), are chiral molecules which were previously tested in their respective bioasays as racemic mixtures. The focus of this study has been to determine the absolute configuration of their natural forms and its relation to stereospecific biological action. DHB was established as the R,R-enantiomer possessing biological activity. Due to an extremely easy racemization of SBT under very mild conditions, enantioselectivity of its transmission and its action at the receptor site appear to be of secondary importance.     

Performance evaluation of neural network architectures: the case of predicting foreign exchange correlations

In the last decade, neural networks have emerged from an esoteric instrument in academic research to a rather common tool assisting auditors, investors, portfolio managers and investment advisors in making critical financial decisions. It is apparent that a better understanding of the network's performance and limitations would help both researchers and practitioners in analysing real‐world problems. Unlike many existing studies which focus on a single type of network architecture, this study evaluates and compares the performance of models based on two competing neural network architectures, the multi‐layered feedforward neural network (MLFN) and general regression neural network (GRNN). Our empirical evaluation measures the network models' strength on the prediction of currency exchange correlation with respect to a variety of statistical tests including RMSE, MAE, U statistic, Theil's decomposition test, Henriksson–Merton market timing test and Fair–Shiller informational content test. Results of experiments suggest that the selection of proper architectural design may contribute directly to the success in neural network forecasting. In addition, market timing tests indicate that both MLFN and GRNN models have economically significant values in predicting the exchange rate correlation. On the other hand, informational content tests discover that the neural network models based on different architectures capture useful information not found in each other and the information sets captured by the two network designs are independent of one another. An auxiliary experiment is developed and confirms the possible synergetic effect from combining forecasts made by the two different network architectures and from incorporating information from an implied correlation model into the neural network forecasts. Implied correlation and random walk models are also included in our empirical experiment for benchmark comparison. Copyright © 2005 John Wiley & Sons, Ltd.     

Chemical communication in invertebrates

Conclusions In conclusion, olfactory pheromones are widespread in nature and control many fundamental aspects of an insect's life. Detailed behavioral observations in the field and laboratory indicate the great complexity of most pheromone communication systems. The preliminary electrophysiological experiments on single olfactory receptor neurons that we have described here, point toward the possibility of unraveling the basic physiological mechanisms underlying these behavioral complexities. This information is directly applicable to many problem areas in chemoreception and could provide a base for the rational use of pheromones in the control of insect pests. *** DIRECT SUPPORT *** A2025171 00003     

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin light-chain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed.     

Intercellular communication in smooth muscle

The functioning of a group of cells as a tissue depends on intercellular communication; an example is the spread of action potentials through intestinal tissue resulting in synchronized contraction. Recent evidence for cell heterogeneity within smooth muscle tissues has renewed research into cell coupling.Electrical coupling is essential for propagation of action potentials in gastrointestinal smooth muscle.Metabolic coupling may be involved in generation of pacemaker activity. This review deals with the role of cell coupling in tissue function and some of the issues discussed are the relationship between electrical synchronization and gap junctions, metabolic coupling, and the role of interstitial cells of Cajal in coupling.