[Separation of undamaged single nerve fibers by using an ultrasonic microscalpel]. / Vydelenie nepovrezhdennykh odinochnykh nervnykh volokon s pomoshch'iu ul'trazvukovogo mikroskal'pelia.

A routine procedure for dissection of single nerve fibres with sharpened sewing needles is rather tiresome and occasionally traumatic because of poor efficiency in cutting interfibrous connective tissue and sticking out patches of it to preparative needles. The described method using microscalpel oscillating with ultrasonic frequency is free from these shortcomings. Voltage clamp tests proved an innocuous character of this method for excitable nodal membrane.

[Localization of the binding site for quaternary derivatives of ajmaline in the Na channel of an excitable membrane]. / O lokalizatsii uchastka sviazyvaniia chetvertichnykh derivatov aimalina v Na-kanale vozbudimoi membrany.

The effects of external or internal application of quaternary derivatives of ajmaline and N-propyl ajmaline (NMA) to the frog nodes of Ranvier were studied by the voltage clamp method. It was established that external application of NMA is much less effective than that of the tertiary amine ajmaline or its quaternary analog N-ethyl ajmaline at comparable concentration. Even at a concentration of 1 mM NMA when applied externally caused only relatively insignificant tonic and use-dependent inhibition of sodium currents. In contrast, internal application of NMA (1 mM) through the cut ends of the fiber led to pronounced use-dependent inhibition of sodium currents. The conclusion is drawn that the binding site for NMA is located in the inner mouth of the Na channels which becomes available for the charged blocker only after opening of the activation gate.

[Differences in the action of Ca2+ ions on a cumulative Na-channel blockade due to tertiary and quaternary amines]. / Razlichie v deistvii ionov Ca2+ na kumuliativnyi blok Na-kanalov, vyzyvaemyi tretichnymi i chetvertichnymi aminami.

In voltage-clamp experiments on frog myelinated fibres it has been established that the increase in Ca2+ concentration from 2 to 20 mM does not effect the use-dependent (cumulative) inhibition of sodium channels (INa) produced by the tertiary local anesthetics (lidocaine, tetracaine, etidocaine) and the quaternary antiarrhythmic drug N-propyl ajmaline (NPA). The NPA-induced inhibition of sodium channels does not undergo any essential changes as the (Ca)0 is raised from 2 to 20 mM. On the contrary, the cumulative blockade produced by the tertiary local anesthetics under such an elevation of the (Ca)0 is sharply reduced. This reduction is caused by the inhibitory action of the (Ca)0 on the local anesthetics-induced transition of sodium channels from the state of rapid to slow inactivation. The (Ca)0 does not affect the interaction of the quaternary NPA with open sodium channels. The data obtained provide evidence in favour of the hypothesis about the existence of the different binding sites responsible for cumulative blockade of the INa induced by tertiary and quaternary amines.

[Differences in the blocking action of benzocaine and amino compounds on batrachotoxin-modified node of Ranvier sodium channels]. / Razlichie v blokruishchem deistvii benzokaina i aminnykh soedinenii na modifitsirovannye batrakhotoksinom natrievye kanaly perekhvata Ranv'e.

Voltage-clamp experiments on the frog Ranvier node have shown that batrachotoxin (BTX) decreases drastically the sensitivity of sodium channels to the blocking action of various tertiary (procaine, trimecaine, ajmalin, strychnine) and quaternary (QX-572, N-propylajmaline) amine drugs but does not affect noticeably sodium channels blockade produced by neutral benzocaine. The inhibition of BTX-modified sodium current by large concentrations of trimecaine (3.5 mM) is time- and voltage-dependent. Neither of the amines used proved to be able to cause frequency-dependent (cummulative) block of modified channels. Unblocking of these channels during washing of the node with Ringer solution proceeds much faster than that of normal channels. On the contrary, restoration of normal and modified currents blocked previously by benzocaine has the same time course. The relationships between "receptors" for BTX and various sodium channel blockers are discussed.

[Stimulus dependent sodium channel blockade in node of Ranvier membranes by the quaternary antiarrhythmic N-propyl ajmaline (neogiluritmal)]. / Stimul-zavisimaia blokada natrievykh kanalov v membrane perekhvata Ranv'e chetvertichnym antiaritmikom n-propyl aimalinom (neogiluritmalem).

The blocking action of neo-gilurytmal (NG), a quaternary derivative of aimalin, on sodium channels was studied in the voltage-clamped node of Ranvier. NG exerted no action on the resting membrane unless the repetitive pulsing was turned on. A series of repetitive depolarizing pulses of short duration (5 ms) produced the accumulating "stimulus-dependent" blockade of sodium channels. The rate and degree of the blockade increased with the increasing of pulse voltage even over the potential range where all the sodium channels were open. Recovery from the blockade occurred within several tens of minutes. Unlike the repetitive pulsing, long-lasting (1 s) depolarization of the membrane produced only a slight increase in the blockade of sodium channels. Elimination of sodium inactivation by aconitine prevented the blocking action of NG. The results of the experiments indicate that NG blocks only the open sodium channels with intact inactivation gate.