scholarly journals Abstract Action Potential Models for Toxin Recognition

2005 ◽  
Vol 6 (4) ◽  
pp. 199-234 ◽  
Author(s):  
James Peterson ◽  
Taufiquar Khan

In this paper, we present a robust methodology using mathematical pattern recognition schemes to detect and classify events in action potentials for recognizing toxins in biological cells. We focus on event detection in action potential via abstraction of information content into a low dimensional feature vector within the constrained computational environment of a biosensor. We use generated families of action potentials from a classic Hodgkin–Huxley model to verify our methodology and build toxin recognition engines. We demonstrate that good recognition rates are achievable with our methodology.

2005 ◽  
Vol 94 (6) ◽  
pp. 4430-4440 ◽  
Author(s):  
Sofija Andjelic ◽  
Vincent Torre

Calcium dynamics in leech neurons were studied using a fast CCD camera. Fluorescence changes (Δ F/ F) of the membrane impermeable calcium indicator Oregon Green were measured. The dye was pressure injected into the soma of neurons under investigation. Δ F/ F caused by a single action potential (AP) in mechanosensory neurons had approximately the same amplitude and time course in the soma and in distal processes. By contrast, in other neurons such as the Anterior Pagoda neuron, the Annulus Erector motoneuron, the L motoneuron, and other motoneurons, APs evoked by passing depolarizing current in the soma produced much larger fluorescence changes in distal processes than in the soma. When APs were evoked by stimulating one distal axon through the root, Δ F/ F was large in all distal processes but very small in the soma. Our results show a clear compartmentalization of calcium dynamics in most leech neurons in which the soma does not give propagating action potentials. In such cells, the soma, while not excitable, can affect information processing by modulating the sites of origin and conduction of AP propagation in distal excitable processes.


2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.


1983 ◽  
Vol 244 (3) ◽  
pp. H341-H350
Author(s):  
C. H. Conrad ◽  
R. G. Mark ◽  
O. H. Bing

We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.


1974 ◽  
Vol 60 (3) ◽  
pp. 653-671
Author(s):  
D. B. SATTELLE

1. A mean resting potential of -53.3 (S.D. ±2.7) mV has been obtained for 23 neurones of the parietal and visceral ganglia of Limnaea stagnalis (L.). Changes in the resting potential of between 28 and 43 mV accompany tenfold changes in [K+0]. A modified constant-field equation accounts for the behaviour of most cells over the range of external potassium concentrations from 0-5 to 10.o mM/1. Mean values have been estimated for [K+1, 56.2 (S.D.± 9-0) mM/1 and PNa/PK, 0-117 (S.D.±0-028). 2. Investigations on the ionic basis of action potential generation have revealed two cell types which can be distinguished according to the behaviour of their action potentials in sodium-free Ringer. Sodium-sensitive cells are unable to support action potentials for more than 8-10 min in the absence of sodium. Sodium slopes of between 29 and 37 mV per decade change in [Na+0] have been found for these cells. Tetrodotoxin (5 x 10-5 M) usually blocks action potentials in these neurones. Calcium-free inger produces a marked reduction in the overshoot potential and calcium slopes of about 18 mV per decade change in [Ca2+o] are found. Manganous chloride only partially reduces the action potential overshoot in these cells at concentrations of 10 mM/l. 3. Sodium-insensitive neurones maintain action potentials in the absence of external sodium. Stimulation only slightly reduces the amplitude of the action potential under these conditions and such cells are readily accessible to potassium ions in the bathing medium. A calcium-slope of 29 mV per decade change in [Ca2+o] has been observed in these cells in the absence of external sodium. 4. It is concluded that both sodium and calcium ions can be involved in the generation of the action potential in neurones of Limnaea stagnate, their relative contribution varying in different cells.


1999 ◽  
Vol 81 (1) ◽  
pp. 408-411 ◽  
Author(s):  
Dax A. Hoffman ◽  
Daniel Johnston

Hoffman, Dax A. and Daniel Johnston. Neuromodulation of dendritic action potentials. J. Neurophysiol. 81: 408–411, 1999. The extent to which regenerative action potentials invade hippocampal CA1 pyramidal dendrites is dependent on both recent activity and distance from the soma. Previously, we have shown that the amplitude of back-propagating dendritic action potentials can be increased by activating either protein kinase A (PKA) or protein kinase C (PKC) and a subsequent depolarizing shift in the activation curve for dendritic K+ channels. Physiologically, an increase in intracellular PKA and PKC would be expected upon activation of β-adrenergic and muscarinic acetylcholine receptors, respectively. Accordingly, we report here that activation of either of these neurotransmitter systems results in an increase in dendritic action-potential amplitude. Activation of the dopaminergic neurotransmitter system, which is also expected to raise intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) and PKA levels, increased action-potential amplitude in only a subpopulation of neurons tested.


1999 ◽  
Vol 277 (2) ◽  
pp. H826-H833 ◽  
Author(s):  
Seiko Tanabe ◽  
Toshio Hata ◽  
Masayasu Hiraoka

To explore a possible ionic basis for the prolonged Q-T interval in women compared with that in men, we investigated the electrophysiological effects of estrogen in isolated guinea pig ventricular myocytes. Action potentials and membrane currents were recorded using the whole cell configuration of the patch-clamp technique. Application of 17β-estradiol (10–30 μM) significantly prolonged the action potential duration (APD) at 20% (APD20) and 90% repolarization (APD90) at stimulation rates of 0.1–2.0 Hz. In the presence of 30 μM 17β-estradiol, APD20 and APD90 at 0.1 Hz were prolonged by 46.2 ± 17.1 and 63.4 ± 11.7% of the control ( n = 5), respectively. In the presence of 30 μM 17β-estradiol the peak inward Ca2+ current ( I CaL) was decreased to 80.1 ± 2.5% of the control ( n = 4) without a shift in its voltage dependence. Application of 30 μM 17β-estradiol decreased the rapidly activating component of the delayed outward K+ current ( I Kr) to 63.4 ± 8% and the slowly activating component ( I Ks) to 65.8 ± 8.7% with respect to the control; the inward rectifier K+ current was barely affected. The results suggest that 17β-estradiol prolonged APD mainly by inhibiting the I Kcomponents I Krand I Ks.


1988 ◽  
Vol 254 (6) ◽  
pp. H1157-H1166 ◽  
Author(s):  
J. A. Wasserstrom ◽  
J. J. Salata

We studied the effects of tetrodotoxin (TTX) and lidocaine on transmembrane action potentials and ionic currents in dog isolated ventricular myocytes. TTX (0.1-1 x 10(-5) M) and lidocaine (0.5-2 x 10(-5) M) decreased action potential duration, but only TTX decreased the maximum rate of depolarization (Vmax). Both TTX (1-2 x 10(-5) M) and lidocaine (2-5 x 10(-5) M) blocked a slowly inactivating toward current in the plateau voltage range. The voltage- and time-dependent characteristics of this current are virtually identical to those described in Purkinje fibers for the slowly inactivating inward Na+ current. In addition, TTX abolished the outward shift in net current at plateau potentials caused by lidocaine alone. Lidocaine had no detectable effect on the slow inward Ca2+ current and the inward K+ current rectifier, Ia. Our results indicate that 1) there is a slowly inactivating inward Na+ current in ventricular cells similar in time, voltage, and TTX sensitivity to that described in Purkinje fibers; 2) both TTX and lidocaine shorten ventricular action potentials by reducing this slowly inactivating Na+ current; 3) lidocaine has no additional actions on other ionic currents that contribute to its ability to abbreviate ventricular action potentials; and 4) although both agents shorten the action potential by the same mechanism, only TTX reduces Vmax. This last point suggests that TTX produces tonic block of Na+ current, whereas lidocaine may produce state-dependent Na+ channel block, namely, blockade of Na+ current only after Na+ channels have already been opened (inactivated-state block).


2015 ◽  
Vol 39 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Javier Rodriguez-Falces

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity.


2003 ◽  
Vol 89 (2) ◽  
pp. 657-664 ◽  
Author(s):  
Robert R. Buss ◽  
Charles W. Bourque ◽  
Pierre Drapeau

The physiological and pharmacological properties of the motoneuron membrane and action potential were investigated in larval zebrafish using whole cell patch current-clamp recording techniques. Action potentials were eliminated in tetrodotoxin, repolarized by tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-AP)-sensitive potassium conductances, and had a cobalt-sensitive, high-threshold calcium component. Depolarizing current injection evoked a brief (approximately 10–30 ms) burst of action potentials that was terminated by strong, outwardly rectifying voltage-activated potassium and calcium-dependent conductances. In the presence of intracellular cesium ions, a prolonged plateau potential often followed brief depolarizations. During larval development (hatching to free-swimming), the resting membrane conductance increased in a population of motoneurons, which tended to reduce the apparent outward rectification of the membrane. The conductances contributing to action potential burst termination are hypothesized to play a role in patterning the synaptically driven motoneuron output in these rapidly swimming fish.


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