Kinetic depolarization effects

As the current correlation function in the time integral has sums over all charge velocities z, effects of cross terms between ionic and molecular motions appear which cannot be identified or separated by electromagnetic measurements. In addition to static solvation and saturation effects on permittivity often considered in biological contexts, Hubbard and Onsager have pointed out "kinetic depolarization" effects which need to be considered. In II, we discuss experimental evidence and implications of the theoretical predictions of such effects. 

The decreases in permittivity when ions are added to a polar solvent were traditionally interpreted in terms of saturation or solvation of local ionic environments (76) until Hubbard and Onsager (77) (78) worked out a continuum theory of the kinetic depolarization effect. This arises from the fact that part of the electric field solvent dipoles near an ion is from the moving ion and similarly for the ion in the field of reorienting dipoles with the consequences that both responses are delayed in proportion to the relaxation time of the solvent polarization. The remarkably simple Hubbard-Onsager expression for the resulting decrement of static (or better limiting low frequency) permittivity can be written... 

Ag/AgCl, which indicates the starting potentials of lithium deposition shift to a positive potential resulting from a depolarizing effect for forming alloys. In comparison with the CVs on the other kind of electrodes, the cathodic current is clearly lower on the Al-Cu alloy electrode. Because these electrodes have same exposed surface areas (about 0.3 cm ) except aluminum electrode (about 0.6 cm ), the size of resistance determined the size of the current. The resistance may come from ohmic resistance and mass transfer resistance. In this case, the slower kinetics of lithium deposition on Al-Cu alloy electrode might have the major influence on the current size. 

Activation is slower in less depolarized membranes and inactivation drains the open (and resting) state more effectively. In fact, real Na" " channels gate by more complex pathways, including several closed states intermediate between R and O, as well as multiple inactivated states. Inactivation from these intermediate states is probably faster than from / , and the entire activation process, in its fully branched entirety, is rich with kinetic possibilities. However, the effects of toxins may be understood in general by the simpler scheme presented in Figure 2. 

Figure 4. Effects of dihydro-brevetoxin B (H2BVTX-B) on Na currents in crayfish axon under voltage-clamp. (A) A family of Na currents in control solution each trace shows the current kinetics responding to a step depolarization (ranging from -90 to -I-100 mV in 10 mV increments). Incomplete inactivation at large depolarizations is normal in this preparation. (B) Na currents after internal perfusion with H2BVTX-B (1.2 a M). inactivation is slower and less complete than in the control, and the current amplitudes are reduced. (C) A plot of current amplitudes at their peak value (Ip o, o) and at steady-state (I A, A for long depolarizations) shows that toxin-mOdified channels (filled symbols) activate at more negative membrane potentials and correspond to a reduced peak Na conductance of the axon (Reproduced with permission from Ref. 31. Copyright 1984 American Society for Pharmacology and Experimental Therapeutics).

Various mechanisms for electret effect formation in anodic oxides have been proposed. Lobushkin and co-workers241,242 assumed that it is caused by electrons captured at deep trap levels in oxides. This point of view was supported by Zudov and Zudova.244,250 Mikho and Koleboshin272 postulated that the surface charge of anodic oxides is caused by dissociation of water molecules at the oxide-electrolyte interface and absorption of OH groups. This mechanism was put forward to explain the restoration of the electret effect by UV irradiation of depolarized samples. Parkhutik and Shershulskii62 assumed that the electret effect is caused by the accumulation of incorporated anions into the growing oxide. They based their conclusions on measurements of the kinetics of Us accumulation in anodic oxides and comparative analyses of the kinetics of chemical composition variation of growing oxides. 

Taken together, the limited experiments conducted using neuronal cell cultures illustrate a distinct difference in the way that pyrethroids modify ion conductance and subsequent neurotransmitter release under resting and depolarized conditions. Continued efforts utilizing recent new tools like automated patch-clamp systems and MEAs to assess the effects of pyrethroids on the kinetics and voltage-dependent gating of ion channels in primary cultures or transfected cells is likely to provide new insight into the neurotoxicity of pyrethroids [79, 82]. 

As with other members of class IB, mexiletine slows the maximal rate of depolarization of the cardiac membrane action potential and exerts a negligible effect on repolarization. Mexiletine demonstrates a rate-dependent blocking action on the sodium channel, with rapid onset and recovery kinetics suggesting that it may be more useful for the control of rapid as opposed to slow ventricular tachyarrhythmias. 

Lidocaine blocks activated and inactivated sodium channels with rapid kinetics (Figure 14-9) the inactivated state block ensures greater effects on cells with long action potentials such as Purkinje and ventricular cells, compared with atrial cells. The rapid kinetics at normal resting potentials result in recovery from block between action potentials and no effect on conduction. The increased inactivation and slower unbinding kinetics result in the selective depression of conduction in depolarized cells. 

This mechanism is kinetically indistinguishable from others. Often dissolution is controlled by the transport rate of either the acid or the depolarizer, whichever is not present in excess (5). The relative concentrations of the control changes depend on the diffusion coefficients as well as the effective reaction equivalents per mole of oxidant. Oxidizing agents which do not require H+ for reduction, such as Fe+, Ce+% Cr+3 are sometimes called depolarizers, but the role of acid in the dissolution is secondary in these cases. 

The separation of the measured effect into ionic contributions requires assumptions on reference ions depending on the nature of the solvent. For acetonitrile solutions, a pattern of consistent solvation numbers is obtained at negligible kinetic depolarization for Li" (4),fVo (4),Br (2),Bu4fV+(0),/"(0),C /07(0) in agreement with those from FTIR measurements for Li., Na and CIO. Reasonable solvation numbers are found for Na ions in FA and DMF both for = 0(6) or 0(4). Independent of the choice... 

To separate kinetic and resistive effects, one can perform experiments at variable scan rate and at different concentrations of electroactive species. As a result, the peak potential separation increases on increasing v and the concentration of the depolarizer, allowing for estimation of the uncompensated resistance from the slope of the peak potential separation versus peak current plot for different analyte concentrations at a given potential scan rate (DuVall and McGreery, 1999, 2000) using the relationship ... 

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