Gromada J, Høy M, Olsen H L, Gotfredsen C F, Buschard K, Rorsman P, Bokvist K
Novo Nordisk A/S, Novo Alle, 2880 Bagsvaerd, Denmark.
Pflugers Arch. 2001 Apr;442(1):19-26. doi: 10.1007/s004240000474.
Somatostatin hyperpolarized rat pancreatic alpha-cells and inhibited spontaneous electrical activity by activating a low-conductance K+ channel (0.9 pS with physiological ionic gradients). This channel was insensitive to tolbutamide (a blocker of ATP-sensitive K+ channels) and apamin (an inhibitor of small-conductance Ca(2+)-activated K+ channels). Channel activation was prevented by pre-treating the cells with pertussis toxin, indicating the involvement of G-proteins. A direct interaction between an inhibitory G-protein and the somatostatin-activated K+ channel is suggested by the finding that intracellular application of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma-S) and the G beta gamma subunit of G-proteins resulted in a transient stimulation of the current. Activation of the K+ current by somatostatin was inhibited by intracellular dialysis with specific antibodies to Gi1/2 and was not seen in cells treated with antisense oligonucleotides against G-proteins of the subtype Gi2. We conclude that somatostatin suppresses alpha-cell electrical activity by a Gi2-protein-dependent mechanism, which culminates in the activation of a sulphonylurea- and apamin-insensitive low-conductance K+ channel.
生长抑素使大鼠胰腺α细胞超极化，并通过激活一种低电导钾通道（在生理离子梯度下为0.9 pS）来抑制自发电活动。该通道对甲苯磺丁脲（一种ATP敏感性钾通道阻滞剂）和蜂毒明肽（一种小电导钙激活钾通道抑制剂）不敏感。用百日咳毒素预处理细胞可阻止通道激活，表明G蛋白参与其中。细胞内应用鸟苷5'-O-(3-硫代三磷酸)（GTPγ-S）和G蛋白的Gβγ亚基导致电流短暂增强，这一发现提示抑制性G蛋白与生长抑素激活的钾通道之间存在直接相互作用。用针对Gi1/2的特异性抗体进行细胞内透析可抑制生长抑素对钾电流的激活，在用针对Gi2亚型G蛋白的反义寡核苷酸处理的细胞中未观察到这种激活。我们得出结论，生长抑素通过一种依赖Gi2蛋白的机制抑制α细胞电活动，该机制最终导致激活一种对磺酰脲类药物和蜂毒明肽不敏感的低电导钾通道。
