Wang X, Greer M A
Department of Physiology, Oregon Health Sciences University, Portland 97201, USA.
Mol Cell Endocrinol. 1995 Mar;109(1):11-8. doi: 10.1016/0303-7207(95)03478-p.
Blocking K+ channels induces hormone secretion in various pituitary cell lines by a mechanism which is not completely delineated. In the present study, we employed the mouse pituitary tumor-derived AtT-20 cell as a model to evaluate this phenomenon. We correlated the effect of the K+ channel-blocker, tetraethylammonium (TEA), on K+ current and membrane potential utilizing whole cell recording, on cytosol Ca2+ ([Ca2+]i) concentration utilizing fura-2, and on ACTH secretion utilizing a perifusion system. TEA inhibited voltage-dependent K+ current and initiated membrane depolarization in a dose-dependent fashion. Divergences in the sensitivity to TEA between voltage-dependent K+ currents and membrane depolarization indicate that voltage-dependent K+ channels are not responsible for TEA-induced depolarization TEA (1-30 mM) also induced a concentration-dependent rise in [Ca2+]i concentration and ACTH secretion, both of which were inhibited by removing medium Ca2+. Our data indicate that TEA inhibits K+ currents and induces membrane depolarization; this opens Ca2+ channels in the plasmalemma, causing a rise in [Ca2+]i which initiates ACTH secretion. Alteration of K+ channel permeability by hormones or neurotransmitters may thus play an important regulatory role in controlling pituitary hormone secretion.
阻断钾离子通道可通过一种尚未完全阐明的机制诱导多种垂体细胞系分泌激素。在本研究中，我们以源自小鼠垂体肿瘤的AtT-20细胞为模型来评估这一现象。我们利用全细胞记录法研究了钾离子通道阻滞剂四乙铵（TEA）对钾离子电流和膜电位的影响，利用fura-2研究了其对胞浆钙离子（[Ca2+]i）浓度的影响，并利用灌流系统研究了其对促肾上腺皮质激素（ACTH）分泌的影响。TEA以剂量依赖性方式抑制电压依赖性钾离子电流并引发膜去极化。电压依赖性钾离子电流与膜去极化对TEA敏感性的差异表明，电压依赖性钾离子通道并非TEA诱导去极化的原因。1-30 mM的TEA还可诱导[Ca2+]i浓度和ACTH分泌呈浓度依赖性升高，去除培养基中的钙离子均可抑制二者升高。我们的数据表明，TEA抑制钾离子电流并诱导膜去极化；这会打开质膜上的钙离子通道，导致[Ca2+]i升高，从而引发ACTH分泌。因此，激素或神经递质引起的钾离子通道通透性改变可能在垂体激素分泌的控制中发挥重要的调节作用。
