On early stages of adult skeletal muscle reinnervation multiple axonal inputs per muscle fiber exist. These excessive inputs need to be eliminated until only one endplate per fiber remains. Synaptic elimination includes decrease of synaptic activity and subsequent retraction of the silent terminals [1]. Previously we have shown that Ca2+ entering the terminal through L-type Ca2+-channels triggers the release of intracellular Ca2+ from ryanodine stores, which in turn leads to depression of ACh release in reinnervated neuromuscular junctions [2]. Ca2+-dependent protein kinase C which is known (along with other substrates) to modulate the activity of voltage-dependent K+-channels (Kv) was considered as a possible target for this Ca2+ signal. Study of electrical activity of regenerating motor synapses was performed 11 days after the mechanical crushing (nembutal (50 mg/kg) i.p. for general and 0.5% lidocaine hydrochloride s.c. for local anaesthesia) of n. peroneus communis, supplying m. extensor digitorum longus in adult mice. Spontaneous and evoked synaptic transmission and its sensitivity to Kv-channels and Ca2+-dependent protein kinase C modulation was examined. Mann-Whitney test was performed for statistical analysis. All data are presented as mean±S.E.M. Blockade of protein kinase C, with chelerytrine (4 μM) and bisindolylmaleimide I (1 μM) showed a significant increase in quantal content (QC) of EPSPs, up to 58±7% and 66±9% respectively (n=71, p<0.05). This increase was very similar to effects of L-type Ca2+-channels blocker nifedipine (10 μM): it caused rapid 60±5% elevation of QC (n=60). But nifedipine applied after chelerytrine was not able to affect amplitude or QC of EPSP`s. QC was 12±1 in control, 18±2 under influence of chelerytrine (p<0.05) but 17±2 under influence of both chelerytrine and nifedipine (n=65). Upregulation of QC caused by blocking the ryanodine receptors with ryanodine (5 μM) was prevented by adding chelerytrine to the bath solution: 8±1 in control, 15±1 after incubation with ryanodine (p<0.05), 10±1 with both ryanodine and chelerytrine (n=67). These results suggest that activation of protein kinase C may be triggered by Ca2+ influx from the intracellular ryanodine stores, which in turn is activated by Ca2+ entering the terminal through L-type Ca2+-channels. Application of Kv-channels blocker 4-aminopyridine (6 μM) was found to greatly increase QC of EPSP`s in newly formed synapses: from 19±2 in control to 30±2 (p<0.05, n=63). Pre-incubation with chelerytrine prevented further enhancement of synaptic transmission by 4-aminopyridine. EPSP`s QC reached 17±2 in control, 30±2 after incubation with chelerytrine (p<0.05) and 30±2 with both chelerytrine and 4-aminopyridine (n=70). The data obtained demonstrate that increased activity of Kv channels controlled by PKC may be the mechanism of Ca2+-dependent inactivation in newly formed synapses.