Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse
Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse
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DOI：
10.1111/j.1469-7793.2001.0141j.x
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发表时间：
2001-02-15
影响因子：
5.5
通讯作者：
Augustine, GJ
中科院分区：
文献类型：
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作者：
Hilfiker, S;Czernik, AJ;Augustine, GJ
1. 采用电生理和显微注射方法研究了环AMP依赖性蛋白激酶A （PKA）在调节鱿鱼巨突触递质释放中的作用。由突触前动作电位诱发的兴奋性突触后电位（EPSPs）不受哺乳动物PKA.3外源性活性催化亚基的突触前注射的影响。相反，突触前注射ki -酰胺（一种高效和特异性抑制PKA的肽）导致epsp的可逆抑制。注射其他几种作为PKA底物的肽也可逆地抑制神经递质释放。这些肽抑制释放的能力与其作为PKA底物的能力相关，这表明这些肽通过与内源性底物竞争活性内源性PKA.5的磷酸化而起作用。我们认为PKA底物的磷酸化在基础条件下维持在相对较高的状态，并且PKA的这种强张性活性在很大程度上是鱿鱼巨大突触前末端诱发神经递质释放所必需的。
1. Electrophysiological and microinjection methods were used to examine the role of cyclic AMP dependent protein kinase A (PKA) in regulating transmitter release at the squid giant synapse.2. Excitatory postsynaptic potentials (EPSPs) evoked by presynaptic action potentials were not affected by presynaptic injection of an exogenous active catalytic subunit of mammalian PKA.3. In contrast, presynaptic injection of PKI-amide, a peptide that inhibits PKA with high potency and specificity, led to a reversible inhibition of EPSPs.4. Injection of several other peptides that serve as substrates for PKA also reversibly inhibited neurotransmitter release. The ability of these peptides to inhibit release was correlated with their ability to serve as PKA substrates, suggesting that these peptides act by competing with endogenous substrates for phosphorylation by active endogenous PKA.5. We suggest that the phosphorylation of PKA substrates is maintained at a relatively high state under basal conditions and that this tonic activity of PKA is to a large degree required fur evoked neurotransmitter release at the squid giant presynaptic terminal.