RESUMEN
Calmodulin inhibitor W-7 did not cause changes in the quantal content of postsynaptic end-plate potentials (EPP) in newly formed synapses, but prevented facilitation of acetylcholine secretion induced by L-type Ca(2+)channels blocker nitrendipine. CaMKII inhibitor KN-62 produced similar effect and suppressed the increase in EPP quantal content caused by blockade of L-type Ca(2+)channels. Phosphatase PP2A inhibitor okadaic acid significantly facilitated secretion in newly formed synapses; the effect was completely blocked by KN-62. In mature synapses, okadaic acid had no effect on transmitter secretion. KN-62 increased EPP quantal content. We hypothesize that CaMKII produced different effects on acetylcholine secretion in mature and immature synapses depending on specificity of calcium signaling and PP2A phosphatase activity.
Asunto(s)
Canales de Calcio Tipo L/metabolismo , Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Acetilcolina/metabolismo , Animales , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Ratones , Placa Motora/efectos de los fármacos , Neurotransmisores/metabolismo , Nitrendipino/farmacología , Ácido Ocadaico/farmacología , Monoéster Fosfórico Hidrolasas/antagonistas & inhibidores , Sulfonamidas/farmacología , Sinapsis/efectos de los fármacosRESUMEN
Nifedipine, a blocker of L-type Ca(2+)-channels, increased quantal content of endplate potentials in newly formed nerve-muscle synapses, while R 24571 (calmodulin inhibitor) and KN 62 (inhibitor of calmodulin-dependent kinase II) did not change it. KN 62 suppressed the increase in quantal content of endplate potentials evoked by nifedipine. Similar to nifedipine, chelerythrine and bisindolylmaleimide I (blockers of protein kinase C) increased quantal content of endplate potentials. In the presence of chelerythrine, nifedipine lost its ability to facilitate secretion of neurotransmitter. 4-Aminopyridine, a blocker of voltage-gated potassium channels, increased quantal content of endplate potentials. In the presence of chelerythrine, 4-aminopyridine induced no additional increase in the quantal content of endplate potentials. In its turn, chelerythrine induced no extra facilitation of secretion in the presence of 4-aminopyridine. It is hypothesized that Ca(2+)-dependent inhibition of secretion results from suppression of calmodulin-dependent kinase II and activation of protein kinase C, which potentiates the work of voltage-gated K(+)-channels.