PubMed · 10966609
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C G Galizia, R Menzel. 2000. Probing the olfactory code.. https://doi.org/10.1038/78741
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The electrophysiological and mechanical effects of HNS-32, a novel azulene-1-carboxamidine derivative with antiarrhythmic activity, were studied in isolated guinea-pig myocardial preparations. HNS-32 (10(-6)-10(-4) mol/l) concentration-dependently decreased the maximum rate of rise (V(max)) of action potential in isolated papillary muscle; the potency was the same or slightly higher than that of disopyramide. At 10(-4) mol/l, HNS-32 also shortened the action potential duration (APD) and depolarized the resting membrane potential; these effects were similar to those of 10(-5) mol/l verapamil. HNS-32 (10(-7)-10(-4) mol/l), as well as verapamil (10(-8)-10(-5) mol/l) and disopyramide (10(-6)-10(-3) mol/l), had concentration-dependent negative chronotropic and negative inotropic effects on isolated right atrial and right ventricular papillary muscle preparations, respectively. The concentration-response relationship for the positive chronotropic effect of isoproterenol was not affected by HNS-32 (10(-5) mol/l). In isolated ventricular myocytes, HNS-32 (10(-6)-10(-4) mol/l) concentration-dependently inhibited the peak amplitude of the L-type Ca(2+) current. These results suggest that NHS-32 has V(max) reducing activity on myocardial tissue, which may be responsible for antiarrhythmic effect. The drug may also have additional effect on the Ca(2+) channel at higher concentrations.
The use of chronically implanted electrodes for neural recordings in small, freely behaving animals poses several unique technical challenges. Because of the need for an extremely lightweight apparatus, chronic recording technology has been limited to manually operated microdrives, despite the advantage of motorized manipulators for positioning electrodes. Here we describe a motorized, miniature chronically implantable microdrive for independently positioning three electrodes in the brain. The electrodes are controlled remotely, avoiding the need to disturb the animal during electrode positioning. The microdrive is approximately 6 mm in diameter, 17 mm high and weighs only 1.5 g, including the headstage preamplifier. Use of the motorized microdrive has produced a ten-fold increase in our data yield compared to those experiments done using a manually operated drive. In addition, we are able to record from multiple single neurons in the behaving animal with signal quality comparable to that seen in a head-fixed anesthetized animal. We also describe a motorized commutator that actively tracks animal rotation based on a measurement of torque in the tether.
By solving the partial differential equations for an axonal segment using a finite element method, the interaction between membrane kinetics and axonal inhomogeneities, measured by their influence on propagated action potentials and stochastic spike trains, is investigated for Morris-Lecar and Hodgkin-Huxley membrane models. To facilitate comparisons of both kinetic models, parameter values are matched to give approximately the same speed for propagated action potentials. In all cases examined, the Morris-Lecar membrane model is more sensitive to geometric inhomogeneities than the comparable Hodgkin-Huxley membrane model. This difference in sensitivity can, in part, be attributed to significant differences in the membrane current supplied by each kinetic model ahead of the action potential. Also, the Morris-Lecar membrane model did not generate reflected action potentials whereas these were observed over a narrow range of geometric parameters for the comparable Hodgkin-Huxley membrane model. Simulations using stochastic spike train input showed that the presence of a sharp flare could significantly modify the statistical characteristics of the spike train output. The behaviour of action potentials governed by Morris-Lecar kinetics were more sensitive to changes in axonal geometry than those generated by comparable Hodgkin-Huxley kinetics. As a consequence of the fine balance between membrane kinetics and axon geometry, local changes in membrane properties, such as those caused by synaptic activity, can be expected to have a strong influence on the behaviour of stochastic spike trains at regions of changing axonal geometry.