Current ionic

While APD/repolarization assays are suggested as one approach to explore the risk for delayed repolarization (ICH S7B guidance), they are generally not widely used at present, likely due to the ease of use (and interpretation) of hERG current assays conpared to AP/repolarization studies in supporting regulatory submission, lack of accepted industry best-standard/practices for APD/repolarization assays, as well as potentially important differences in ventricular repolarization across species (vs. humans). For exanple, it is well established that I,j/hERG plays a prominent role in 

FIGURE 9.2 Multiple approaches possible for in vitro evaluation of electrophysiologic effects on cardiac cells and tissnes. 

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Researchers at the MoneU Center (Philadelphia, Pennsylvania) are using a variety of electrophysical and biochemical techniques to characterize the ionic currents produced in taste and olfactory receptor cells by chemical stimuli. These studies are concerned with the identification and pharmacology of the active ion channels and mode of production. One of the techniques employed by the MoneU researchers is that of "patch clamp." This method aUows for the study of the electrical properties of smaU patches of the ceU membrane. The program at MoneU has determined that odors stimulate intraceUular enzymes to produce cycUc adenosine 3, 5 -monophosphate (cAMP). This production of cAMP promotes opening of the ion channel, aUowing cations to enter and excite the ceU. MoneU s future studies wiU focus on the connection of cAMP, and the production of the electrical response to the brain. The patch clamp technique also may be a method to study the specificity of receptor ceUs to different odors, as weU as the adaptation to prolonged stimulation (3). 

An electrolyte (3) common to both materials, through which an ionic current flows... 

An interesting consequence of the influence of fluid conductivity is the observation that ionic currents can be diminished by geometry. For... 

Transport numbers are intended to measure the fraction of the total ionic current carried by an ion in an electrolyte as it migrates under the influence of an applied electric field. In essence, transport numbers are an indication of the relative ability of an ion to carry charge. The classical way to measure transport numbers is to pass a current between two electrodes contained in separate compartments of a two-compartment cell These two compartments are separated by a barrier that only allows the passage of ions. After a known amount of charge has passed, the composition and/or mass of the electrolytes in the two compartments are analyzed. Erom these data the fraction of the charge transported by the cation and the anion can be calculated. Transport numbers obtained by this method are measured with respect to an external reference point (i.e., the separator), and, therefore, are often referred to as external transport numbers. Two variations of the above method, the Moving Boundary method [66] and the Eiittorff method [66-69], have been used to measure cation (tR+) and anion (tx ) transport numbers in ionic liquids, and these data are listed in Table 3.6-7. 

The presence of dissolved ions facilitates the passage of an ionic current through the solution. 

The conductivity of the environment low conductivity hinders the ionic current flow hence distilled water is less corrosive than a solution of sodium chloride with the same pH and dissolved oxygen content. 

Most organic solvents, except for alcohol, have reasonably low ionic conductivity and hence do not support electro-chemically corrosion to any significant extent. Steel is commonly used except in systems in which water can separate and where the conductivity is sufficient to permit the flow of ionic current. 

Anodic passivation also allows titanium to be employed as a Jig for aluminium anodising baths ", because the protective anodic film formed on titanium allows passage of electronic current to the metal contact while virtually suppressing flow of ionic current through the anodically-formed surface film. This aspect is discussed in more detail in relation to special applications. 

When two different metals are immersed in the same electrolyte solution they will usually exhibit different electrode potentials. If they are then connected by an electronic conductor there will be a tendency for the potentials of the two metals to move towards one another they are said to mutually polarise. The polarisation will be accompanied by a flow of ionic current through the solution from the more negative metal (the anode) to the more positive metal (the cathode), and electrons will be transferred through the conductor from the anode to the cathode. Thus the cathode will benefit from the supply of electrons, in that it will dissolve at a reduced rate. It is said to be cathodically protected . Conversely, in supplying electrons to the cathode the anode will be consumed more rapidly, and thus will act as a sacrificial anode. 

Fig. 15. Mass spectral pattern Polytherms of total pressure (P) and ionic currents of gaseous components in the form of ions separating from a TaiOs -NH4HF2 system versus heating temperature (after Agulyansky et al. [114]).

Fig. 92. Mass spectral parameters pressure (p in torr) and ionic currents (J in relative units) of Li2NbOF5 (A), Na2NbOFs (B) and K2NbOFs (C) versus temperature in °C (after Agulyansky et ah, [383]). Numbers on the curves correspond to ions as shown in Fig. 91.

The ionic current intensity corresponding to the peak at 169 amu was analyzed under isothermal and polythermal conditions [383]. It was found that in a gaseous atmosphere, the intensity changes are in correlation with the CO content and in negative correlation with the C02 content. The presence of CO in vacuum systems equipped with heating elements is usually related to thermo-cycling and desorption of CO by nickel atoms [386]. Based on the above, the presence of NbF4+ ions in mass spectra is most probably related to the niobium reduction process, which can be represented as follows ... 

Separators serve two primary functions while having to keep the positive electrode physically apart from the negative in order to prevent any electronic current passing between them, they also have to permit an ionic current with least, possible hindrance. These two opposing requirements are best met by a compromise a porous nonconductor. 

Porosity of a separator is defined as the ratio of void volume to apparent geometric volume. High porosity is desirable for unhindered ionic current flow. 

The electrical resistance exerted by a separator on the ionic current is defined as the total resistance of the separator filled with electrolyte minus the resistance of a layer of electrolyte of equal thickness, but without the separator. The separator resistance has to be considered as an increment over the electrolyte resistance. 

The prime requirements for the separators in alkaline storage batteries are on the one hand to maintain durably the distance between the electrodes, and on the other to permit the ionic current flow in as unhindered a manner as possible. Since the electrolyte participates only indirectly in the electrochemical reactions, and serves mainly as ion-transport medium, no excess of electrolyte is required, i.e., the electrodes can be spaced closely together in order not to suffer unnecessary power loss through additional electrolyte resistance. The separator is generally flat, without ribs. It has to be sufficiently absorbent and it also has to retain the electrolyte by capillary forces. The porosity should be at a maximum to keep the electrical resistance low (see Sec. 9.1.2.3) the pore size is governed by the risk of electronic shorts. For systems where the electrode substance... 

Improvement of the ionic current by fast transport in the electrodes. High electronic mobility and low electronic concentration favor fast chemical diffusion in electrodes by building up high internal electric fields [14]. This effect enhances the diffusion of ions toward and away from the solid electrolyte and allows the establishment of high current densities for the battery. 

Antiarrhythmic Drugs. Figure 1 Transmembrane ionic currents of the cardiac action potential. In the middle of the figure, a typical cardiac action potential is shown as can be obtained from the ventricular myocardium (upper trace). Below, the contribution of the various transmembrane currents is indicated. Currents below the zeroline are inward currents above the zero line are outward fluxes. In the left column the name of the current is given and in the right column the possible clone redrawn and modified after [5]. 

Antiarrhythmic treatment is based upon modulation of the ionic currents mentioned above. A principal problem with this therapy is that the electrophysiology of all cells is targeted and not specifically the arrhythmogenic focus. As a consequence, all antiar-rhythmics acting at transmembrane ionic channels possess a risk for elicitation of arrhythmia (= proar-rhythmic risk). 

The patch-clamp technique is based on the formation of a high resistance seal (109-10lon) between the tip of a glass micropipette and the cell membrane it touches (gigaohm-seal). This technique allows recordings of ionic currents through single ion channels in the intact cell membrane and in isolated membrane patches at a... 

Catterall WA (2000) From ionic currents to molecular mechanisms the structure and function of voltage-gated sodium channels. Neuron 26 13-25... 

Figure 1. A depiction of the several different ionic currents necessary for the acute function of neuromuscular transmission in the skeletal motor and the efferent autonomic nervous system. The boxed current designations are associated, by the arrows, with those cellular regions where their physiological role is most evident, although these currents often exist in other regions of the cell. = neurotransmitter-activated current ...

A breakthrough in cell modelling occurred with the work of the British scientists. Sir Alan L. Hodgkin and Sir Andrew F. Huxley, for which they were in 1963 (jointly with Sir John C. Eccles) awarded the Nobel prize. Their new electrical models calculated the changes in membrane potential on the basis of the underlying ionic currents. 

In porous separators the pore radii are large compared to the size of molecules. Hence, interaction between the electrolyte and the pore walls has practically no qualitative effects on the ionic current through the separator the transport numbers of the individuaf ions have the same vafues in the pores as in the bulk electrolyte, hi swollen membranes the specific interaction between individuaf ions and macromofecufes is very pronounced. Hence, these membranes often exhibit sefectivity in the sense that different ions are affected differentfy in their migration. As a resuft, the transport numbers of the ions in the membrane differ from those in the efectrofyte outside the membrane. In the limiting case, certain types of ion are arrested completely, and the membrane is called permselective (see Chapter 5). 

Influence on Electrolyte Conductivity In porous separators the ionic current passes through the liquid electrolyte present in the separator pores. Therefore, the electrolyte s resistance in the pores has to be calculated for known values of porosity of the separator and of conductivity, o, of the free liquid electrolyte. Such a calculation is highly complex in the general case. Consider the very simple model where a separator of thickness d has cylindrical pores of radius r which are parallel and completely electrolyte-filled (Fig. 18.2). Let / be the pore length and N the number of pores (all calculations refer to the unit surface area of the separator). The ratio p = Ud (where P = cos a > 1) characterizes the tilt of the pores and is called the tortuosity factor of the pores. The total pore volume is given by NnrH, the porosity by... 

This technique has been used to investigate the effect of the photoactivation of rose bengal on /wa/K in isolated rabbit ventricular myocytes (Shattock and Matsuura, 1993). Using this procedure, 5 min exposure to illuminated rose bengal reduced 7Na/K to 60% of control at 0 mV and to 75% of control at -75 mV. In the absence of extracellular potassium, no active ionic currents remain... 

Shattock, M.J., Hearse, D.J. and Matsuura, H. (1990). Ionic currents underlying orudant stress-induced arrhythmias. In Ionic Currents and Ischemia (eds. J. Vereecke, P.P. van... 

Fig. 4.28. Ionic current / and concentration of nitrogen atoms [N] as functions of the grid potential of the discharge device (the source of nitrogen atoms).

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