Admittance change of squid axon during action potentials. Change in capacitive component due to sodium currents.

Since the discovery of Cole and Curtis (1938. Nature (Lond.). 142:209 and 1939. J. Gen. Physiol. 22:649) that the imaginary components, i.e., capacitive and inductive components, of the admittance of squid axon membrane remained unchanged during the action potential, there have been numerous studies on impedance and admittance characteristics of nerves. First of all, it is now known that the dielectric capacitance of the membrane is frequency dependent. Second, the recent observation of gating currents indicates that dipolar molecules may be involved in the onset of ionic currents. Under these circumstances, the author felt it necessary to reinvestigate the membrane admittance characteristics of nerve axons. The measurements by Cole and Curtis were performed mainly at 20 kHz, indicating that their observation was limited only to the passive membrane capacitance. To detect the change in the capacitive component during the action potential, we performed transient admittance measurements at lower frequencies. However, the frequency range of the measurements was restricted because of the short duration of the normal action potential. In addition, a change in the inductive component obscured the low frequency behavior of the capacitance. To use wider frequency range and simplify the system by eliminating the inductive component, the potassium current was blocked by tetraethyl ammonium, and the increase in the capacitive component was reinvestigated during the long action potential. The admittance change under this condition was found to be mostly capacitive, and conductance change was very small. The increase in the capacitive component was from 1.0 to 1.23 muF/cm2.     

Effects of bath resistance on action potentials in the squid giant axon: myocardial implications.

This study presents a simplified version of the quasi-one-dimensional theory (Wu, J., E. A. Johnson, and J. M. Kootsey. 1996. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys. J. 71:2427-2439) with two components of the extracellular current, along and perpendicular to the axis, and a simulation and its experimental confirmation for the giant axon of the squid. By extending the one-dimensional core conductor cable equations, this theory predicts, as confirmed by the experiment, that the shapes of the intracellular and the extracellular action potentials are related to the resistance of the bath. Such a result was previously only expected by the field theories. The correlation between the shapes of the intracellular and the extracellular potentials of the giant axon of the squid resembles that observed during the anisotropic propagation of excitation in cardiac muscle. Therefore, this study not only develops a quasi-one-dimensional theory for a squid axon, but also provides one possible factor contributing to the anisotropic propagation of action potentials in cardiac muscle.     

Spontaneous action potentials due to channel fluctuations.

A theoretical and numerical analysis of the Hodgkin-Huxley equations with the inclusion of stochastic channel dynamics is presented. It is shown that the system can be approximated by a one-dimensional bistable Langevin equation. Spontaneous action potentials can arise from the channel fluctuations and are analogous to escape by a particle over a potential barrier. The mean firing rate can be calculated using Kramers' classic result for barrier escape. The probability density function of the interspike intervals can also be estimated. The analytical results compare favorably with numerical simulations of the complete stochastic system.     

Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials

Neuronal activity influences myelination of the brain, but the molecular mechanisms involved are largely unknown. Here, we report that oligodendrocyte progenitor cells (OPCs) express functional adenosine receptors, which are activated in response to action potential firing. Adenosine acts as a potent neuron-glial transmitter to inhibit OPC proliferation, stimulate differentiation, and promote the formation of myelin. This neuron-glial signal provides a molecular mechanism for promoting oligodendrocyte development and myelination in response to impulse activity and may help resolve controversy on the opposite effects of impulse activity on myelination in the central and peripheral nervous systems.     

Simulated propagation of cardiac action potentials.

We have used numerical methods for solving cable equations, combined with previously published mathematical models for the membrane properties of ventricular and Purkinje cells, to simulate the propagation of cardiac action potentials along a unidimensional strand. Two types of inhomogeneities have been simulated and the results compared with experimentally observed disturbances in cardiac action potential propagation. Changes in the membrane model for regions of the strand were introduced to simulate regions of decreased excitability. Regional changes in the intercellular coupling were also studied. The results illustrate and help to explain the disturbances in propagation which have been reported to occur at regions of decreased excitability, regions with changing action potential duration, or regions with changing intercellular coupling. The propagational disturbances seen at all of these regions are discussed in terms of the changing electrical load imposed upon the propagating impulse.     

Detecting action potentials in neuronal populations with calcium imaging.

The study of neural circuits requires methods for simultaneously recording the activity of populations of neurons. Here, using calcium imaging of neocortical brain slices we take advantage of the ubiquitous distribution of calcium channels in neurons to develop a method to reconstruct the action potentials occurring in a population of neurons. Combining calcium imaging with whole-cell or perforated patch recordings from neurons loaded with acetoxymethyl ester or potassium salt forms of calcium indicators, we demonstrate that each action potential produces a stereotyped calcium transient in the somata of pyramidal neurons. These signals are detectable without averaging, and the signal-to-noise is sufficient to carry out a reconstruction of the spiking pattern of hundreds of neurons, up to relatively high firing frequencies. This technique could in principle be applied systematically to follow the activity of neuronal populations in vitro and in vivo.     

Generation of action potentials in a mathematical model of corticotrophs.

Corticotropin-releasing hormone (CRH) is an important regulator of adrenocorticotropin (ACTH) secretion from pituitary corticotroph cells. The intracellular signaling system that underlies this process involves modulation of voltage-sensitive Ca2+ channel activity, which leads to the generation of Ca2+ action potentials and influx of Ca2+. However, the mechanisms by which Ca2+ channel activity is modulated in corticotrophs are not currently known. We investigated this process in a Hodgkin-Huxley-type mathematical model of corticotroph plasma membrane electrical responses. We found that an increase in the L-type Ca2+ current was sufficient to generate action potentials from a previously resting state of the model. The increase in the L-type current could be elicited by either a shift in the voltage dependence of the current toward more negative potentials, or by an increase in the conductance of the current. Although either of these mechanisms is potentially responsible for the generation of action potentials, previous experimental evidence favors the former mechanism, with the magnitude of the shift required being consistent with the experimental findings. The model also shows that the T-type Ca2+ current plays a role in setting the excitability of the plasma membrane, but does not appear to contribute in a dynamic manner to action potential generation. Inhibition of a K+ conductance that is active at rest also affects the excitability of the plasma membrane.     

De novo complex chromosomal rearrangement in a woman with recurrent spontaneous abortion and one healthy daughter

Summary Although rare, complex chromosomal rearrangements have been reported in the literature. The result is multiple congenital malformations in the offspring and recurrent spontaneous abortion. Chromosome 7 is usually involved, but in our patient chromosome 18 was involved.     

Ionic mechanism of action of a spin-labeled local anesthetic on squid axon membranes.

The ionic mechanism of action of a spin-labeled local anesthetic (SLA), 2-[N-methyl-N-(2,2,6,6-tetramethylpiperidonooxyl)]-ethyl 4-ethoxylbenzoate, was studied by means of voltage clamp technique with squid giant axons in comparison with the parent compound without spin label moiety, 2-(N,N-dimethyl)ethyl 4-ethoxylbenzoate (GS-01). Like other local anesthetics, they suppressed both sodium and potassium conductance increases. However, three remarkable differences have been noted between SLA and GS-01: (1) SLA is more effective than GS-01 in suppressing the sodium and potassium conductance increases; (2) SLA induces a potassium inactivation, whereas GS-01 is lacking this ability; (3) SLA has no effect on the time to peak sodium current, whereas GS-01 prolongs it. GS-01 resembles procaine with respect to (2) and (3) above. SLA will become a useful probe for the study of the molecular mechanism of local anesthetic aciton and of ionic channel function.     

Effects of external ions on membrane potentials of a crayfish giant axon

Transmembrane potentials in the crayfish giant axon have been investigated as a function of the concentration of normally occurring external cations. Results have been compared with data already available for the lobster and squid giant axons. The magnitude of the action potential was shown to be a linear function of the log of the external sodium concentration, as would be predicted for an ideal sodium electrode. The resting potential is an inverse function of the external potassium concentration, but behaves as an ideal potassium electrode only at the higher external concentrations of potassium. Decrease in external calcium results in a decrease in both resting potential and action potential; an increase in external calcium above normal has no effect on magnitude of transmembrane potentials. Magnesium can partially substitute for calcium in the maintenance of normal action potential magnitude, but appears to have very little effect on resting potential. All ionic effects studied are completely reversible. The results are in generally good agreement with data presently available for the lobster giant axon and for the squid giant axon.     

The effects of potassium and sodium ions on the resting and action potentials of the cockroach giant axon

The effects of varying the potassium and sodium concentrations in the bathing fluid on the resting and action potentials of the cockroach giant axon have been examined by means of intracellular microelectrodes. Plotting the resting potentials against the logarithms of the external potassium concentrations resulted in a straight line in the concentrations higher than about 20 mM. The decrease in the sodium concentration had no appreciable effect on the resting potential, but effectively depressed the action potential. Plotting the reversed potentials against the logarithms of the external sodium concentrations resulted in a straight line, which diverged only slightly from the theoretically expected straight line having a slope of 59 mV for a tenfold change in sodium. The rate of rise of the action potential was decreased very effectively by the sodium-deficient solution. It can safely be said that the overall result constitutes strong evidence for the essential validity of the sodium theory in the cockroach giant axon.     

The ionic regulation of action potentials in the axon of a stretch receptor neuron of the stick insect (Carausius morosus)

Summary The ionic requirements for the action potentials recorded from the axon of the dorsal longitudinal stretch receptor inCarausius morosus have been studied using extracellular electrodes.In the intact preparation prolonged exposure to sodium-free, calcium-free, or magnesium-free salines produces no observable change in the amplitude of action potentials. Similarly, tetrodotoxin (1×10^–6 M) and cobaltous chloride (1×10^–2 M) are both ineffective in blocking the action potentials.In preparations in which the ionic barrier has been disrupted by removal of the nerve sheath the action potentials show sodium dependence. They are sustained in high sodium salines (150 mM) but are reversibly abolished in sodium-free salines. They are also reversibly abolished in 1×10^–6 M TTX, but unaffected by calcium-free or magnesium-free salines, or by cobaltous chloride (1×10^–2 M).It is concluded that the action currents in the axon of the stretch receptor are carried by sodium ions.     

Cortical potentials evoked to response to a signal to make a memory-guided saccade

The difference in parameters of visually guided and memory-guided saccades was shown. Increase in the memory-guided saccade latency as compared to that of the visually guided saccades may indicate the deceleration of saccadic programming on the basis of information extraction from the memory. The comparison of parameters and topography of evoked components N1 and P1 of the evoked potential on the signal to make a memory- or visually guided saccade suggests that the early stage of the saccade programming associated with the space information processing is performed predominantly with top-down attention mechanism before the memory-guided saccade and bottom-up mechanism before the visually guided saccade. The findings show that the increase in the latency of the memory-guided saccades is connected with decision making at the central stage of the saccade programming. We proposed that wave N2, which develops in the middle of the latent period of the memory-guided saccades, is correlated with this process. Topography and spatial dynamics of components N1, P1 and N2 testify that the memory-guided saccade programming is controlled by the frontal mediothalamic system of selective attention and left-hemispheric brain mechanisms of motor attention.     

Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway.

Mechanisms that regulate axon branch stability are largely unknown. Genome-wide analyses of Rho GTPase activating protein (RhoGAP) function in Drosophila using RNA interference identified p190 RhoGAP as essential for axon stability in mushroom body neurons, the olfactory learning and memory center. p190 inactivation leads to axon branch retraction, a phenotype mimicked by activation of GTPase RhoA and its effector kinase Drok and modulated by the level and phosphorylation of myosin regulatory light chain. Thus, there exists a retraction pathway from RhoA to myosin in maturing neurons, which is normally repressed by p190. Local regulation of p190 could control the structural plasticity of neurons. Indeed, genetic evidence supports negative regulation of p190 by integrin and Src, both implicated in neural plasticity.