Na+ Currents

Antiepileptics Na+, Ca2+ channels GABA receptors l Na+currents l Ca2+ currents GABA receptor activity l Excitability of peripheral and central neurons l Release of excitatory neurotransmitters Sedation, dizziness, cognitive impairment, ataxia, hepatotoxicity, thrombocytopenia... 

Antidepressants Noradrenaline/5-HT transporters Na+, K+ channels l Noradrenaline/ 5-HT reuptake l Na+ currents t K+ currents l Excitability of peripheral and central neurons Cardiac arrhythmia, myocardial infarction, sedation, nausea, dry mouth, constipation, dizziness, sleep disturbance, blurred vision... 

In addition to inhibiting fast voltage-dependent Na+ currents, many anticonvulsants also suppress persistent Na+ currents, in some cases even more efficiently. This mechanism may also be important in the anticonvulsant action of these substances because persistent Na+ currents are thought to give rise to high frequency burst discharges in some neurons. 

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).

Figure 5. Multiple actions of toxin II from Ammonia sulcata (ATX II) on voltage-clamped Na currents (Ij ) from amphibian myelinated nerve. This stabilizer toxin works in a dose-dependent manner to inhibit channel inactivation see bottom panel) and, as a consequence, delay the time of peak current see top panel). The reduction of peak current amplitude does not result directly from these kinetic alterations and is not observed with all stabilizers (Reproduced with permission from Ref. 39. Copyright 1981 SPPIF).

Stabilizers bind at a site separate from those of traditional activators and of ciguatoxin-brevetoxin, but they exert a synergistic action on both types of activators (J5, 42). This action potentiates the activators and generally increases their efficacy, yielding larger depolarizations at lower doses 42) it occurs uniquely with the peptide stabilizers and not with ions or oxidants that also slow the inactivation of Na current 37). 

Certain occluders also discriminate among Na channels from neuronal and skeletal muscle. But in this case the blocking ligands are small peptides, the x-conotoxins from the mollusc Conus geo aphus. This molecule binds tightly to muscle Na channels, effectively reducing Na current (55 see Figure 6A), and also can displace bound... 

Inert gas beams allow the chemistry of a surface to be studied by SIMS without modification by the bombarding species. The achievable values of source brightness allow pA currents into spot diameters of approximately 50 pm for dynamic SIMS, or nA currents into spot diameters < 5 pm for imaging SIMS. For greater spatial resolution a different, higher-brightness source must be used. 

W Van Driessche, D Erlij. (1983). Noise analysis of inward and outward Na+ currents across the apical border of ouabain-treated frog skin. Pfluegers Arch 398 179-188. 

Fig. 14. The 1-H line at 6 K in n+ GaAsiSi implanted with a 500 nA current of 190 keV protons. The spectral resolution is 0.4 cm 1, (a) as implanted, (b) after 20 min. annealing at 200°C. (c) after additional 20 min. annealing at 400°C. The apparent increase of the absorption coefficient in (c) is due to the diffusion of hydrogen throughout the Si-doped layer. B. Pajot et al., Mat. Res. Soc. Symp. Proc, 104, 345 (1988). Materials Research Society.

C. Class Ic Greater sodium current depression (blocks the fast inward Na current in heart muscle and Purkinje fibers, and slows the rate of t of phase 0 of the action potential)... 

Class III—drugs that prolong the action potential duration molecules that either block outward K+ currents or augment inward Na currents... 

Classes I, III, and IV all involve transmembrane ion channels Classes I and III involve Na+ channels. Class I compounds are designed to block cardiac Na channels in a voltage-dependent manner, similar to local anesthetics. Not surprisingly, many of these Class I agents are either local anesthetics or are structurally based on local anesthetics. Class I compounds include procainamide (7.15), disopyramide (7.16), amiodarone (7.17), lido-caine (7.5), tocainide (7.18), mexiletine (7.19), and flecainide (7.20). The majority of these compounds possess two or three of the fundamental structural building blocks found within local anesthetics. Propranolol (7.21) is the prototypic Class II agent. Class III compounds include molecules that block outward K channels, such as sotalol (7.22) and dofetilide (7.23), and molecules that enhance an inward Na current, such as... 

Ethosuximide is most commonly used antiepileptic agent in the treatment of petitmal epilepsy. It acts on thalamocortical system by selectively suppressing T current without affecting other types of Ca " or Na" currents. It is completely absorbed from gastrointestinal tract and present in plasma in free form and approximately 20% is excreted unchanged in urine and remaining portion is metabolized in liver. 

Brau ME et al Effect of drugs used for neuropathic pain management on tetrodotoxin-resistant Na+ currents in rat sensory neurons. Anesthesiology 2001 94 137. [PMID 11135733]... 

Brau, M. E., Branitzki, P., Olschewski, A., Vogel, W., Hempelmann, G. Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics, Anest. Analg. 2000, 91, 1499-1505. 

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