Calcium-dependent phosphatase calcineurin downregulates evoked neurotransmitter release in neuromuscular junctions of mice
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We have shown in neuromuscular synapses of mice that inhibition of calcium- and calmodulin-dependent phosphatase calcineurin by cyclosporine A or calcineurin-inhibiting peptide results in a considerable increase in the quantum content of evoked endplate potentials (EPPs) during a short rhythmic train (50 Hz for 1 s). This increase was completely blocked by nitrendipine (a blocker of voltage-dependent calcium channels of the L-type) or inhibition of ryanodine receptors by TMB-8 or ryanodine. The quantum content of single EPPs increased in the presence of an activator of L-type calcium channels, S(-) Bay K 8644. In the presence of this drug, cyclosporine A was unable to further increase the quantum content of EPPs. We concluded that calcineurin during normal functioning of motor synapses of mice inhibits evoked secretion via a decrease in calcium influx via L-type channels and calcium release via ryanodine receptors from intracellular stores.
Keywordscalcineurin evoked activity quantum content L-type calcium channels ryanodine receptors cyclosporine A
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