Yamashita N, Shibuya N, Ogata E
Proc Natl Acad Sci U S A. 1986 Aug;83(16):6198-202. doi: 10.1073/pnas.83.16.6198.
Membrane electrical properties and the response to somatostatin were examined in dissociated human pituitary adenoma cells that secrete growth hormone (GH). Under current clamp condition with a patch electrode, the resting potential was -52.4 +/- 8.0 mV, and spontaneous action potentials were observed in 58% of the cells. Under voltage clamp condition an outward K+ current, a tetrodotoxin-sensitive Na+ current, and a Ca2+ current were observed. Cobalt ions suppressed the Ca2+ current. The threshold of Ca2+ current activation was about -60 mV. Somatostatin elicited a membrane hyperpolarization associated with increased membrane permeability in these cells. The reversal potential of somatostatin-induced hyperpolarization was -78.4 +/- 4.3 mV in 6 mM K+ medium and -97.2 +/- 6.4 mV in 3 mM K+ medium. These reversal potential values and a shift with the external K+ concentration indicated that membrane hyperpolarization was caused by increased permeability to K+. The hyperpolarized membrane potential induced by somatostatin was -63.6 +/- 5.9 mV in the standard medium. This level was subthreshold for Ca2+ and Na+ currents and was sufficient to inhibit spontaneous action potentials. Hormone secretion was significantly suppressed by somatostatin and cobalt ions. Therefore, we suggest that Ca2+ entering the cell through voltage-dependent channels are playing an important role for GH secretion and that somatostatin suppresses GH secretion by blocking Ca2+ currents. Finally, we discuss other possibilities for the inhibitory effect of somatostatin on GH secretion.
在分泌生长激素（GH）的离体人垂体腺瘤细胞中检测了膜电特性以及对生长抑素的反应。在使用膜片电极的电流钳制条件下，静息电位为-52.4±8.0 mV，58%的细胞中观察到自发动作电位。在电压钳制条件下，观察到外向K⁺电流、河豚毒素敏感的Na⁺电流和Ca²⁺电流。钴离子抑制Ca²⁺电流。Ca²⁺电流激活的阈值约为-60 mV。生长抑素在这些细胞中引起膜超极化并伴有膜通透性增加。在6 mM K⁺培养基中，生长抑素诱导的超极化的反转电位为-78.4±4.3 mV，在3 mM K⁺培养基中为-97.2±6.4 mV。这些反转电位值以及随外部K⁺浓度的变化表明，膜超极化是由K⁺通透性增加引起的。在标准培养基中，生长抑素诱导的超极化膜电位为-63.6±5.9 mV。该水平低于Ca²⁺和Na⁺电流的阈值，足以抑制自发动作电位。生长抑素和钴离子显著抑制激素分泌。因此，我们认为通过电压依赖性通道进入细胞的Ca²⁺对GH分泌起重要作用，并且生长抑素通过阻断Ca²⁺电流来抑制GH分泌。最后，我们讨论了生长抑素对GH分泌抑制作用的其他可能性。
