Beaumont V, Zucker R S
Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Nat Neurosci. 2000 Feb;3(2):133-41. doi: 10.1038/72072.
Presynaptic activation of adenylyl cyclase and subsequent generation of cAMP represent an important mechanism in the modulation of synaptic transmission. In many cases, short- to medium-term modulation of synaptic strength by cAMP is due to activation of protein kinase A and subsequent covalent modification of presynaptic ion channels or synaptic proteins. Here we show that presynaptic cAMP generation via serotonin receptor activation directly modulated hyperpolarization-activated cation channels (Ih channels) in axons. This modulation of Ih produced an increase in synaptic strength that could not be explained solely by depolarization of the presynaptic membrane. These studies identify a mechanism by which cAMP and Ih regulate synaptic plasticity.
腺苷酸环化酶的突触前激活以及随后cAMP的产生是调节突触传递的重要机制。在许多情况下，cAMP对突触强度的短期至中期调节是由于蛋白激酶A的激活以及随后突触前离子通道或突触蛋白的共价修饰。在这里，我们表明，通过5-羟色胺受体激活产生的突触前cAMP直接调节轴突中的超极化激活阳离子通道（Ih通道）。Ih的这种调节导致突触强度增加，这不能仅由突触前膜的去极化来解释。这些研究确定了一种cAMP和Ih调节突触可塑性的机制。
