Suppression of mediator secretion in murine neogenic motor synapses with the participation of L-type Ca<Superscript>2+</Superscript>-channels and ryanodine receptors

L-type Ca²⁺-channel blockers, verapamil (5 μM) and nifedipine (10 μM), have increased the quantum composition of endplate potentials (EPP) and the level of induced rhythmic activity of neogenic synapses. L-type Ca²⁺-channel activator BAY K 8644 (1 μM) has a decreased mediator secretion level. Nifedipine (10 μM) has not changed the frequency and amplitude of diminutive EPPs in the dormant state or during potassium depolarization. Blocking of the prejunctional ryanodine receptor with ryanodine (10 μM) led to an increase in the single EPP quantum composition that was qualitatively similar to nifedipine and verapamil, but more marked, and also caused the reinforcement of mediator release during the rhythmic EPP salvo. Ryanodine receptor activation with ryanodine (1 μM) resulted in reduction of the quantum composition of single and rhythmic EPPs. This effect was partially prevented with nifedipine (10 μM).     

Effect of damage to the parietal associative cortex on the function of acquired motor coordination in dogs

The effect of ablation of the parietal associative cortex on the performance of a complex food instrumental reaction was studied in dogs. The reaction consisted in two movements of the forelimb which were of similar pattern, but differed by their coordination. The first one was the lifting and holding of the paw at a required level for a required time, with the head in natural position (lifted), and the second one was the same movement of the paw with the head bent down for feeding, i.e. a new coordination, for the natural coordination consists in lowering of the forelimb associated with lowering of the head. During two sessions after the lesion, both reactions became irregular (so that the dogs performed only one of two movements or none). In the course of four months, the precision of the first movement was reduced, the amplitude of lifting the paw and duration of holding it were diminished. The new coordination persisted after ablation of the parietal associative cortex, though the holding (fixation) of the paw was less perfect. As was shown before by one of the present authors (M. E. Ioffe), lesion of the sensorimotor cortex resulted in profound disturbance of acquired coordination.     

Facilitation and Depression of Neuromuscular Transmission under Conditions of Blockade of Ryanodine Receptors

In our experiments on mice, end-plate currents (EPC) evoked by stimulation of the phrenic nerve were intracellularly recorded in neuromuscular synaptic junctions of the phrenic muscle. We studied the effects of a specific blocker of ryanodine receptors, ryanodine (10 to 20 M), on the amplitude and time parameters of EPC under conditions of tetanic facilitation and depression of synaptic transmission at frequencies of stimulation of 4 to 200 sec^-1. Ryanodine inhibited facilitation at stimulation frequencies of 7 to 70 sec^-1 (with maximum effect at 20 sec^-1) and accelerated depression. In the presence of ryanodine, an initial rundown of the EPC amplitude in the course of depression of transmission increased at high frequencies of stimulation (50 to 100 sec^-1), whereas the EPC amplitude at the plateau level decreased already at low frequencies (4 to 7 sec^-1). We concluded that the changes in facilitation and depression resulted from blocking of the presynaptic ryanodine receptors by ryanodine. It seems probable that calcium release from the calcium stores in murine motor terminals is a factor involved in the control of processes of transmitter secretion during short-term rhythmic activation of the junction.     

Effects of dantrolene and ryanodine on the evoked activity of neuromuscular synapses in mice

Ryanodine was shown to potentiate in a frequency-dependent manner a late phase of initial facilitation increasing the EPP amplitude for 15%-40% in a fixed interval 140-400 ms after the first EPP in the discharge. Dantrolene prevented the ryanodine induced increase of the late phase of facilitation, decreased 2-fold the amplitude and quantum content of single EPPs, augmented initial depression, blocked facilitation in 50% of synapses. Only in presence of dantrolene, the ryanodine's ability to increase the EPPs quantum content and early phase of the EPP facilitation in rhythmically active synapses, was revealed.