Effects of IKs channel inhibitors in insulin-secreting INS-1 cells
Effects of IKs channel inhibitors in insulin-secreting INS-1 cells
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DOI：
10.1007/s00424-005-1479-2
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发表时间：
2005-12-01
影响因子：
4.5
通讯作者：
Lang, F
中科院分区：
文献类型：
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作者：
Ullrich, S;Su, JP;Lang, F
钾通道调节胰岛素分泌。K-ATP通道的关闭导致膜去极化，从而触发Ca2+内流并刺激胰岛素分泌。随后激活的K+通道终止分泌。我们研究了KCNQ1通道是否在胰腺β细胞中表达，并分析了它们的功能作用。RT/PCR在INS-1细胞中检测到KCNQ1而非KCNE1通道的细胞mRNA。采用膜片钳法研究了KCNQ1通道抑制剂两种磺胺类似物293B和HMR1556对电压激活的外向整流K+电流的影响。结果表明，293B对-70 ~ +50 mV电压脉冲诱导的全细胞外向电流有60%的抑制作用，IC50为37 μ m，而另一种磺胺类似物HMR1556对外向电流有48%的抑制作用，IC50为7 μ m，而氯胺醇293B对甲苯丁酰胺敏感的K-ATP通道没有影响。电流注入引起的动作电位变宽，重极化后的动作电位被293B减弱。胰岛素分泌在存在而不存在tolbuamide的情况下显著增加293B。这些结果表明，293B-和hmr1556敏感通道可能与其他电压激活的K+通道一起影响动作电位持续时间和频率，从而影响胰岛素分泌。
Potassium channels regulate insulin secretion. The closure of K-ATP channels leads to membrane depolarisation, which triggers Ca2+ influx and stimulates insulin secretion. The subsequent activation of K+ channels terminates secretion. We examined whether KCNQ1 channels are expressed in pancreatic beta-cells and analysed their functional role. Using RT/PCR cellular mRNA of KCNQ1 but not of KCNE1 channels was detected in INS-1 cells. Effects of two sulfonamide analogues, 293B and HMR1556, inhibitors of KCNQ1 channels, were examined on voltage-activated outwardly rectifying K+ currents using the patch-clamp method. It was found that 293B inhibited 60% of whole-cell outward currents induced by voltage pulses from -70 to +50 mV with a concentration for half-maximal inhibition (IC50) of 37 mu M. The other sulfonamide analogue HMR1556 inhibited 48% of the outward current with an IC50 of 7 mu M. The chromanol 293B had no effect on tolbutamide-sensitive K-ATP channels. Action potentials induced by current injections were broadened and after-repolarisation was attenuated by 293B. Insulin secretion in the presence but not in the absence of tolbutamide was significantly increased by 293B. These results suggest that 293B- and HMR1556-sensitive channels, probably in concert with other voltage-activated K+ channels, influence action potential duration and frequency and thus insulin secretion.