cAMP and forskolin inhibit potassium currents in rat taste receptor cells by different mechanisms
cAMP and forskolin inhibit potassium currents in rat taste receptor cells by different mechanisms
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DOI：
10.1152/ajpcell.1997.272.6.c2005
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发表时间：
1997-06-01
影响因子：
5.5
通讯作者：
Chen, YS
中科院分区：
文献类型：
--
作者：
Herness, MS;Sun, XD;Chen, YS
在味觉传导中，已经提出当甜味刺激升高时关闭钾通道或当苦味刺激抑制时打开cAMP门控阳离子通道。这些实验用标准膜片钳技术检查cAMP对来自后部味觉受体细胞的全细胞电流的影响。通过移液管给药、膜渗透类似物[8-（4-氯苯硫基）-cAMP（CPT-cAMP）和二丁酰-cAMP]或磷酸二酯酶抑制[3-异丁基-1-甲基黄嘌呤（IBMX）]升高胞浆cAMP，对外向钾电流产生高达33%的不良可逆抑制。出乎意料的是，中高浓度的毛喉素（>5 μ M）深刻和可逆地抑制这些电流（95%），大大加速失活动力学。1，9-二脱氧毛喉素，一种无效的腺苷酸环化酶激活剂，同样有效。激酶抑制剂有效地阻断了由IBMX或CPT-cAMP产生的cAMP升高的作用，但没有阻断这些毛喉素的作用。然而，在低浓度（5 μ M），毛喉素磷酸化依赖性的方式减少钾电流。总的来说，这些数据表明，cAMP产生磷酸化依赖性抑制外向钾电流，但毛喉素的行动是独立的cAMP或磷酸化，除了在低浓度。cAMP也能有效地改变味觉动作电位的波形，这意味着它可以改变味觉信息向大脑的传递。
In gustatory transduction, adenosine 3',5'-cyclic monophosphate (cAMP) has been suggested to close potassium channels when elevated by sweet stimuli or to open cAMP-gated cation channels when depressed by bitter stimuli. These experiments examine the effect of cAMP on whole cell currents from posterior taste receptor cells with standard patch-clamp techniques. Elevating cytosolic cAMP by pipette administration, membrane-permeant analogs [8-(4-chlorophenylthio)-cAMP (CPT-cAMP) and dibutyryl-cAMP], or by phosphodiesterase inhibition [3-isobutyl-1-methylxanthine (IBMX)] produced poorly reversible inhibitions of outward potassium currents by up to 33%. Unexpectedly, middle to high concentrations of forskolin (>5 mu M) profoundly and reversibly inhibited these currents (95%) with greatly accelerated inactivation kinetics. 1,9-Dideoxyforskolin, an ineffective activator of adenylate cyclase, was similarly potent. Kinase inhibitors effectively blocked the effects of cAMP elevations produced by IBMX or CPT-cAMP but did not block these forskolin actions. However, at low concentrations (5 mu M), forskolin reduced potassium currents in a phosphorylation-dependent manner. Collectively, these data suggest that cAMP pro duces a phosphorylation- dependent inhibition of outward potassium currents but that forskolin's actions are independent of cAMP or phosphorylation except at low concentration. cAMP was also effective in altering the waveform of the gustatory action potential, implying it may modify transmission of gustatory information to the brain.