IBMX
腺苷酸环化酶
蛋白激酶A
福斯科林
化学
生物物理学
抑制性突触后电位
葡萄孢霉素
河豚毒素
磷酸二酯酶抑制剂
通道阻滞剂
膜电位
钙调蛋白
生物
激酶
内分泌学
生物化学
钙
信号转导
受体
有机化学
酶
作者
Satoru Kondo,Alain Marty
标识
DOI:10.1113/jphysiol.1997.sp021849
摘要
1. Cellular mechanisms underlying the enhancement by noradrenaline (NA) of inhibitory postsynaptic currents (IPSCs) were studied at inhibitory synapses in the molecular layer of the cerebellum. IPSCs were obtained from stellate cells in rat cerebellar slices using tight‐seal whole‐cell recording. 2. Miniature IPSCs (mIPSCs) were recorded in the presence of tetrodotoxin (TTX; 100 nM). NA (10 microM) markedly increased the frequency of mIPSCs, but did not alter their mean amplitude. Bath application of the inhibitor of adenylyl cyclase 9‐(tetrahydro‐2'‐furyl) adenine (SQ 22,536; 300 microM), of the wide spectrum protein kinase inhibitor staurosporine (1 microM), and of the Rp‐diastereomer of adenosine‐3',5'‐cyclic monophosphothioate (Rp‐cAMPS; 500 microM), a specific inhibitor of cAMP‐dependent protein kinase (PKA), inhibited the mIPSC frequency increase induced by NA. 3. The increase in mIPSC frequency was not attenuated by Cd2+ (100 microM), a blocker of voltage dependent calcium channels. However, after a 12‐15 min pre‐incubation in Ca(2+)‐free saline, the effect of NA on mIPSCs was markedly inhibited. If Ca2+ ions were readmitted in the presence of NA, enhancement of the mIPSC frequency was largely restored. 4. Application of the membrane permeant analogue of cAMP, 8‐Br‐cAMP (1 mM), together with the inhibitor of cAMP phosphodiesterase, 3‐isobutyl‐1‐methylxanthine (IBMX; 100 microM), caused a frequency increase of mIPSCs. Forskolin also mimicked the stimulatory effect of NA on mIPSC frequency. The effects of both 8‐Br‐cAMP and forskolin persisted in Ca(2+)‐free saline, suggesting that the modulation of transmitter release does not require Ca2+ influx. 5. On the whole, the results indicate that the potentiation of mIPSC frequency by NA is mediated through the sequential activation of adenylyl cyclase and protein kinase A (PKA), and that PKA modulates the vesicle release mechanism rather than Ca2+ influx. The lack of effect of NA after prolonged incubation in Ca(2+)‐free solution may be due to an inhibition of adenylyl cyclase by a gradual lowering of the cytosolic presynaptic Ca2+ concentration.
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