Proceedings of the Royal Society of London Series B-Containing Papers of Abiological Character最新文献

Adopting principles learnt from insect vision we have constructed model of a general-purpose front-end visual system for motion detection that is designed to operate in parallel along each photoreceptor axis with only local connections. The model is also designed to assist electrophysiological analysis of visual processing because it puts the response to a moving scene into sets of template responses similar to the distribution of activity among different neurons. An earlier template model divided the visual image into the fields of adjacent receptors, measured as intensity or receptor modulation at small increments of time. As soon as we used this model with natural scenes, however, we found that we had to look at changes in intensity, not intensity itself. Running the new model also generated new insights into the effects of very fast motion, of blurring the image, and the value of lateral inhibition. We also experimented with ways of measuring the angular velocity of the image moving across the eye. The camera eye is moved at a known speed and the range to objects is calculated from the angular velocity of contrasts moving across the receptor array. The original template model is modified so that contrast is saturated in a new representation of the original image data. This reduces the 8-bit grey-scale image to a log, 3 = 1.6-bit image, which becomes the input to a look-up table of templates. The output consists of groups of responding templates in specific ratios that define the input features, and these ratios lead into types of invariance at a higher level of further logic. At any stage, there can be persistent parallel inputs from all earlier stages. This design would enable groups of templates to be tuned to different expected situations, such as different velocities, different directions and different types of edges.

In the receptor-transducer model of pharmacological agonism, rejection of the traditional assumption that receptor molecules are in vast excess of transducer molecules permits the receptors to become distributed among unbound, bound and complexed states. Under these conditions, agonist affinities are liable to be overestimated when the method of irreversible receptor antagonism is used. Graphical tests have been developed to detect distribution, and these were applied to experimental data from the interaction between 5-HT and phenoxybenzamine on aortic tissue. Significant receptor distribution was not detected by the method. However, in the model it was assumed that there was a linear relation between the concentration of ternary complex and pharmacological effect. If this relation was replaced with a saturable one the effect of receptor distribution would be masked. The implications for pharmacologists and medicinal chemists are discussed.

Flukes of cetaceans are capable of absorbing energy from ocean waves for propulsion. The extent of this energy absorption is demonstrated by considering the flukes of an immature fin whale, Balaenoptera physalus. In a fully developed seaway corresponding to a wind speed of 20 knots (around Beaufort force 5) and at a low swimming speed, of 2.5 m s-1, this whale was able to absorb up to 25% of its required propulsive power in head seas and 33% of propulsive power in following seas. Consequences of wave-energy absorption for energetics of cetacean migrations are discussed.

Computer simulations in which selection acts on a quantitative character show that the randomness of mutations can contribute significantly to evolutionary divergence between populations. In different populations, different advantageous mutations occur, and are selected to fixation, so that the populations diverge even when they are initially identical, and are subject to identical selection. This stochastic process is distinct from random genetic drift. In some circumstances (large populations or strong selection, or both) mutational order can be greatly more important than random drift in bringing about divergence. It can generate a 'disconnection' between evolution at the phenotypic and genotypic levels, and can give rise to a rough 'molecular clock', albeit episodic, that is driven by selection. In the absence of selection, mutational order has little or no effect.

The actions of the polychlorocycloalkane insecticide heptachlor, and its epoxide metabolite, were examined on GABA receptors in insects and vertebrates. Electrophysiological experiments on the cell body of the cockroach (Periplaneta americana) fast coxal depressor motor neuron (Df), and GABA-activated 36Cl- uptake experiments on microsacs prepared from cockroach ventral nerve cords showed that both heptachlor and heptachlor epoxide blocked functional GABA receptors. The block appeared to be non-competitive and was voltage-independent over the membrane potential range -75 mV to -110 mV. There was no significant difference between the potencies of heptachlor and heptachlor epoxide in the functional assays for insect GABA receptors. Both compounds inhibited [35S]-t-butylbicyclophosphorothionate [( 35S]TBPS) binding in insects and vertebrates. The findings provide further evidence for block of an insect GABA receptor/Cl- channel by the cyclodiene class of polychlorocycloalkanes, and reveal differences in the insecticide-[35S]TBPS binding site interactions of insects and vertebrates.

The hypothesis that calcium release from the sarcoplasmic reticulum in cardiac muscle is induced by rises in free cytosolic calcium (Fabiato 1983, Am. J. Physiol 245) allows the possibility that the release could be at least partly regenerative. There would then be a non-linear relation between calcium current and calcium release. We have investigated this possibility in a single-cell version of the rabbit-atrial model developed by Hilgemann & Noble (1987, Proc. R. Soc. Lond. B 230). The model predicts different voltage ranges of activation for calcium-dependent processes (like the sodium-calcium exchange current, contraction or Fura-2 signals) and the calcium current, in agreement with the experimental results obtained by Earm et al. (1990, Proc. R. Soc. Lond. B 240) on exchange current tails, Cannell et al. (1987, Science, Wash. 238) by using Fura-2 signals, and Fedida et al. (1987, J. Physiol., Lond. 385) and Talo et al. (1988, Biology of isolated adult cardiac myocytes) by using contraction. However, when the Fura-2 concentration is sufficiently high (greater than 200 microM) the activation ranges become very similar as the buffering properties of Fura-2 are sufficient to remove the regenerative effect. It is therefore important to allow for the buffering properties of calcium indicators when investigating the correlation between calcium current and calcium release.

To investigate the underlying ionic mechanism of the late plateau phase of the action potential in rabbit atrium the whole-cell patch-clamp technique with intracellular perfusion was used. We recorded the inward current during repolarizations following a brief 2 ms depolarizing pulse to +40 mV from a holding potential of between -70 and -80 mV. The development of this current coincides with the onset of the late plateau phase of the action potential. Peak activation of the current occurs about 10 ms from the beginning of the depolarizing pulse, and it decays spontaneously with a slow timecourse. Its voltage dependency from -40 mV to +40 mV shows very steep activation (-40 to -20 mV) and shows almost the same maximum magnitude between -10 mV and +40 mV. This behaviour is quite different from that of the calcium current. The inward current and the late plateau phase of the action potential were both abolished by the application of 5 mM EGTA, 1 microM ryanodine and by reducing the Na+ gradient. The fully activated current-voltage relation of the inward current was plotted as the difference current before and after treatment with Ryanodine, Diltiazem, 20 mM Na+ inside or 30% Na+ outside and shows an exponential voltage dependence with the largest magnitude of the current occurring at negative potentials. The current-voltage (I-V) curve was well fitted by the Na-Ca exchange equation, i = A exp (-(1 - r)EF/RT). The results suggest that the inward current contributes to the generation of the late plateau phase of the rabbit atrial action potential, and is activated by intracellular calcium released from the sarcoplasmic reticulum. Sarcoplasmic reticulum calcium release appears to be triggered both by the membrane voltage and by the calcium current. It is concluded that the inward current is generated by Na-Ca exchange.

We have used the calcium indicator dye arsenazo III, together with a photodiode array, to record intracellular calcium changes simultaneously from all regions of individual guinea pig cerebellar Purkinje cells in slices. The optical signals, recorded with millisecond time resolution, are good indicators of calcium-dependent electrical events. For many cells the sensitivity of the recordings was high enough to detect signals from each array element without averaging. Consequently, it was possible to use these signals to follow the complex spatial and temporal patterns of plateau and spike potentials. Calcium entry corresponding to action potentials was detected from all parts of the dendritic field including the fine spiny branchlets, demonstrating that calcium action potentials spread over the entire arbor. Usually, the entire dendritic tree fired at once. But sometimes only restricted areas had signals at any one moment with transients detected in different regions at other times. In one cell, six separate zones were distinguished. These results show that calcium action potentials could be regenerative in some dendrites and could fail to propagate into others. Signals from plateau potentials were also detected from extensive areas in the dendritic field but were always smaller than those caused by a burst of action potentials.

Immunolabelling with a 5 nm gold probe was used to localize dystrophin at the ultrastructural level in human muscle. The primary antibody was monoclonal, raised against a segment (amino acids 1181-1388) from the rod domain of dystrophin. The antibody (Dy4/6D3) is specific for dystrophin and shows no immunoreactivity with any protein from mdx mouse muscle or from patients with a gene deletion spanning part of the molecule recognized by the antibody (Nicholson et al. 1989 a; England et al. 1990). Using this antibody, labelling was almost entirely confined to a narrow 75 nm rim at the periphery of the muscle fibres. Histograms of the distance from the gold probe to the cytoplasmic face of the plasma membrane and of the distance between gold probes (nearest neighbour in a plane parallel with the plasma membrane) displayed modes at approximately 15 nm and 120 nm, respectively. The distribution of the probe was the same in longitudinal and transverse sections of the muscle. These observations suggest that the rod portion of the dystrophin molecule is normally arranged close to the cytoplasmic face of the plasma membrane and that the molecules form an interconnecting network. Labelling was not associated with the transverse tubular system.