Role of stored calcium in the regulation of neurotransmitter quantum size.

Release of stored calcium ions during activation of ryanodine receptors with ryanodine or caffeine elevates the mean amplitude of spontaneous miniature end-plate potentials. Blockade of these receptors with selective antagonists abolishes this effect. Preliminary loading of the motor nerve terminals with intracellular calcium buffer EGTA-AM, but not with BAPTA-AM, also completely prevented the ryanodine-induced increment of miniature end-plate potential amplitude probably induced by the release of stored calcium. Vesamicol, a selective blocker of acetylcholine transport into vesicles, prevented the ryanodine-induced increment of the mean amplitude of miniature end-plate potentials. This increment was 2-fold more pronounced after preliminary blockade of protein kinase C with chelerythrine and was completely abolished by blockade of protein kinase A with H-89.

Effect of fast and slow calcium buffers on induced secretion of neurotransmitter.

Loading of mouse motor nerve terminals with EGTA-AM, but not with BAPTA-AM, inhibited the release of the neurotransmitter in response to stimulation of the nerve with rare (0.3 Hz) "single" pulses. During rhythmic stimulation with short (50 EPP) high-frequency (20 Hz) series, BAPTA-AM buffer modified burst pattern in a dose-dependent manner: it replaced the phase of initial facilitation by persistent depression of secretion and decreased its plateau level at the end of the burst. In contrast, loading of the nerve terminals with EGTA-AM buffer produced no effect on the phase of initial facilitation, but decreased the plateau level to the same degree as BAPTA-AM did. Probably, the different effects of both buffers on secretion of neurotransmitter reflect peculiarities of involvement of fast and slow Ca(2+)signals of motor terminals in single and rhythmic release of the neurotransmitter.

Digoxin facilitates neuromuscular transmission in mouse diaphragm.

Low concentration of digoxin (3 nM) facilitated spontaneous and evoked release of neurotransmitter acetylcholine thereby increasing the frequency of miniature end-plate potentials, amplitude of single end-plate potentials, their quantum content and the plateau level in the bursts during stimulation of the phrenic nerve at rates of 4, 7, and 50 Hz. These effects were prevented by blockade of ryanodine receptors with ryanodine (10-20 microM).

[Study of neurotrophic effects of yashaltin mud in experimental model of denervation-reinnervation syndrome of shank muscles in mice].

On the experimental model of denervation-reinnervation syndrome of mouse shank muscles neurotrophic effects of jashaltinsky medicinal mud were studied. In experimental mice therapeutic mud has been applied on the small back, tail and rib areas of the body 10 days after nerve crushing. On day 11 after nerve crushing a stable reproduction of a compound nerve action potential with constant amplitude was revealed in repetitive (50 Hz) nerve stimulation.

[Dual action of intracellularly released calcium on the quantal mediator secretion].

The mice diaphragm muscle and microelectrode technique were used to check the influence of ryanodine (0.5 mcM) on spontaneous and evoked mediator release under conditions of potassium depolarization (8-16 mM [K+]ex or rhythmic (4-100 Hz) stimulation of motor nerve terminals. Weak tonic calcium loading (by muscle exposition to 8 mM [K+]ex) caused a two-fold frequency increase if miniature and plate potentials (MEPPs), which was returned to the basal level by subsequent application of ryanodine. This inhibitory effect of ryanodine was blocked by apamin (500 nM) a blocker of K+(Ca)-channels. A greater calcium load of terminals (in solution with 16 mM [K+]ex) caused a 15-fold increase of MEPPs frequency. Subsequent ryanodine application caused an additional 2-3-fold increase of MEPPs frequency. During rhythmic activity of motor synapses, ryanodine was able to decrease the amplitude of EPP by 60% at plateau phase at short low frequency (4 Hz) of discharges and to increase the amplitude of EPP by 60-150% at high frequency (70-100 Hz) of discharges. It is concluded that rynodine induced calcium release from intraterminal Ca2+-stores can influence dual: excitatory or inhibitory, action on spontaneous and evoked mediator release, due to different intraterminal calcium loads and regimen of synaptic activity.

[Effects of dantrolene and ryanodine on the evoked activity of neuromuscular synapses in mice]. / Vyzvannaia aktivnost' nervno-myshechnykh sinapsov myshi na fone deistviia dantrolena i rianodina.

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.