The blocking action of mecamylamine on different types of nicotinic acetylcholine receptors (nAChRs) has been extensively studied and used as a tool to characterize the nAChRs from different synapses. However, mechanism of mecamylamine action was not fully explored for all types of nAChRs. In the present study, we provide brief description of the mecamylamine action on muscle nAChRs expressed at the frog neuromuscular junction. In this preparation mecamylamine block of nAChRs was accompanied by a use-dependent block relief induced by membrane depolarization combined with the activation of nAChRs by endogenous agonist acetylcholine (ACh). Further, three kinetic models of possible mecamylamine interaction with nAChRs were analyzed including simple open channel block, symmetrical trapping block and asymmetrical trapping block. This analysis suggested that mecamylamine action could be described on the basis of trapping mechanism, when the antagonist remained inside the channel even in the absence of bound agonist. Such receptors with trapped mecamylamine inside were predicted to have a closing rate constant about three times faster than resting one and a fast voltage-dependent unblocking rate constant. Specific experimental conditions and morphological organization of the neuromuscular synapses were considered to simulate time course of the mecamylamine block development. Thus, likewise for the neuronal nAChRs, the trapping mechanism determined the action of mecamylamine on synaptic neuromuscular currents evoked by the endogenous agonist acetylcholine (ACh), however specific morphological organization of the synaptic transmission delayed time development of the currents block.

Nicotinic cholinergic receptors can be blocked by both competitive and noncompetitive blocking agents of cholinoreceptors interacting with different regions of ionic channels [1]. Noncompetitive blocking agents may be divided into two subgroups: simple blocking agents of open channels and trapping blocking agents, which were originally described for glutamate receptors [2][3][4][5]. Earlier, we showed in the study on chromaffin rat cells that mecamilamine, a well-known neuronal blocking agent of channels, blocked neuronal cholinoreceptors by the trapping mechanism [6]. This blockade is characterized by unblocking during membrane depolarization and activation of receptors by an agonist [4,6].The neuromuscular junction is a common model for studying the action of ionic-channel blocking agents [7,8]. Earlier [9], it was hypothesized that mecamilamine can block channels in a neuromuscular synapse as a simple blocking agent; however, the trapping mechanism has not been studied yet. Hence, we assessed the mechanism of the mecamilamine effect on the receptor-channel complex of muscle cholinoreceptors.Experiments were carried out using an isolated neuromuscular preparation (sciatic nerve-sartorius muscle) of Rana ridibunda frogs using the standard technique of two-electrode potential fixation described earlier [10]. After infrequent nerve stimulations ( f = 0.05 Hz), mecamilamine at concentrations of 5-20 µ M induced dose-dependent decrease in the amplitude and the decay time constant of evoked endplate currents (EECs). These effects were washed out slowly. A typical experiment with 20 µ M mecamilamine is shown on Fig. 1. It was estimated after approximating averaged dose-effect relationships with Hill's equation that, at -70 mV, I C 50 = 7.8 µ M and n H = 1.2 ( n = 9) . Hill's constant was practically the same as for neuronal cholinoreceptors ( n H = 1.1 [6]), which indicated that the channel was blocked by a single molecule of the blocking agent, whereas the concentration at which the blocking-agent effect was half the maximum ( I C 50 ) for muscle cholinoreceptors was considerably higher than that for neuronal receptors (0.34 µ M [6]). The latter suggests that mecamilamine has a smaller blocking effect on muscle cholinoreceptors.With respect to its EEC time-amplitude characteristics, mecamilamine is analogous to a desensitization promoter or a slow blocking agent of open channels, whose characteristic property is the enhancement of the inhibiting effect upon increasing the frequency of nerve stimulation [10][11][12]. However, our experiments with mecamilamine showed that the increase in the frequency of nerve stimulation to 10 Hz did not induce additional changes in current amplitudes, which indicates another action mechanism of this compound.The mecamilamine effect in the neuromuscular synapse appeared to be potential-sensitive, which is confirmed by a decrease in I C 50 during membrane hyperpolarization (Fig. 2). On the basis of this relationship, we calculated the relative depth of the mecamilamine binding site in ...

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One of the main problems of wood as filler in the production of composite materials based on mineral binder is "cement poisons". Article presents the results of research of the processes of "cement poisons" removal from wood raw material for the production of cement-bonded particleboards. In the research process the treatment of wood raw material was carried out in two ways: by boiling of the crushed wood and by ultrasonic treatment in water. It has been found that ultrasonic treatment significantly intensifies and increases the extraction of water-soluble sugars and, thus, causes an increase of the strength characteristics of cement-bonded particleboards. The conducted research shows the possibility of improvement of the technology of production of cement-bonded particleboards with the aim of improving their performance without significant capital investment.