Single sodium channels, effects

Song JH, Narahashi T (1996) Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels. Brain Res 712 258-264... 

Figure 4. Effects of 60 pM (+)-trans tetramethrin on single sodium channels in an inside-out membrane patch excised from a neuroblastoma cell (N1E-115 line). A, sample records of sodium channel currents (inward deflections) associated with step depolarizations from -90 mV to -50 mV. B, as in A, but after application of tetramethrin to the internal surface of the membrane. C, current amplitude histogram in the control. D, as in C, but after application of tetramethrin. (Reproduced with permission from ref. 31. Copyright 1983 Elsevier.) Continued on next page.

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

Lidocaine Sodium channel bl(xkade Hepatic Local irritation, infusion effects Topical or single IV doses for local nerve block... 

Intoxication with DDT results in ataxia, loss of coordination, convulsions, and hyperexcitation of insects and mammals. Various regions of the nervous system were stimulated to discharge repetitively either in response to a single stimulus or spontaneously. These included sensory cells, synapses, and nerve fibers (2.3.36.37). Repetitive after-discharges in nerve fibers were due to an increase in the depolarizing (negative) after-potential by DDT (M, 39). Repetitive responses in neuromuscular junctions have been shown to originate in presynaptic nerve terminals (40). It appears that DDT and pyrethroids exert similar effects on the nerve membrane sodium channel (41). Detailed analyses as described below clearly show that this is actually the case. 

Cardiovascular Intravenous procainamide had a prodysrhythmic effect when it was given as a single 1000 mg bolus during an electrophysiological study in a patient with myotonic dystrophy type 1 [SO J. During ventricular pacing, ventricular tachycardia and fibrillation occurred and required DC cardioversion. By slowing cardiac conduction, procainamide, as do other sodium channel blockers, worsens abnormalities already present in the hearts of patients with myotonic dystrophy t)q)e 1. 

The choice of the most penalizing single failure depends on the accident type. After considerations about a LIPOSO break inducing a pump seizure risk, the single failure retained was a deterministic fuel cladding failure in the hottest core channel during the LIPOSO scenario. Indeed, the subsequent fission gas release could a priori, disturb the sodium flow, increase its boiling risk from the unfavourable core power / flow ratio due to the pipe break, while a reactivity effect by sodium void could be inserted. 

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