Lee Suk-Ho, Lee Eun Hae, Ryu Shin Young, Rhim Hyewhon, Baek Hye-Jung, Lim Wonil, Ho Won-Kyung
Department of Physiology, Seoul National University, College of Medicine, Seoul, Korea.
Neuroendocrinology. 2003 Nov;78(5):260-9. doi: 10.1159/000074447.
The frequency of spontaneous action potentials (SAP) is important in the regulation of hormone secretion. The decrease in K(+) conductance is known as a primary mechanism for increasing SAP frequency. To investigate the nature of K(+) channels that contribute to the frequency regulation of the SAP in rat clonal pituitary GH(3) cells, the effect of various K(+) channel blockers on the SAP and membrane currents were recorded using the patch-clamp technique. A classical inward rectifying K(+) channel blocker, Cs(+) (5 mM), caused an increase in firing frequency and depolarization in after-hyperpolarization (AHP) voltage. An ETHER-A-GO-GO(ERG) type K(+) channel blocker, E-4031 (5 microM), caused no significant effect on the SAP. Tetraethylammonium (TEA, 10 mM) decreased firing frequency and increased the duration of SAP. These effects were not changed by the presence of high concentration of Ca(2+) buffer (10 mM EGTA or BAPTA) in pipette solutions. In voltage-clamp experiments, Cs(+) and E-4031 did not affect outwardly rectifying K(+) currents, but significantly inhibited inwardly rectifying K(+) currents recorded in isotonic K(+) solution. However, the kinetics of Cs(+)-sensitive current and E-4031-sensitive current were distinctive: the time to peak was more immediate and the decay rate was slower in Cs(+)-sensitive current than in E-4031-sensitive current. These results imply that Cs(+) and E-4031 inhibit the distinct components of inwardly rectifying K(+) currents, and that the contribution of the Cs(+)-sensitive current can be immediate on repolarization and can last more effectively over pacemaking potential range than E-4031-sensitive current.
自发动作电位（SAP）的频率在激素分泌调节中很重要。钾离子（K⁺）电导降低是增加SAP频率的主要机制。为了研究在大鼠垂体克隆GH(3)细胞中对SAP频率调节有贡献的K⁺通道的性质，使用膜片钳技术记录了各种K⁺通道阻滞剂对SAP和膜电流的影响。一种经典的内向整流K⁺通道阻滞剂，铯离子（Cs⁺，5 mM），导致放电频率增加和超极化后电位（AHP）电压去极化。一种醚 - A - 去 - 去（ERG）型K⁺通道阻滞剂，E - 4031（5 μM），对SAP没有显著影响。四乙铵（TEA，10 mM）降低了放电频率并增加了SAP的持续时间。在移液管溶液中存在高浓度的钙离子（Ca²⁺）缓冲剂（10 mM乙二醇双四乙酸或乙二醇双（2 - 氨基乙氧基）四乙酸）时，这些效应没有改变。在电压钳实验中，Cs⁺和E - 4031不影响外向整流K⁺电流，但显著抑制在等渗K⁺溶液中记录的内向整流K⁺电流。然而，Cs⁺敏感电流和E - 4031敏感电流的动力学是不同的：Cs⁺敏感电流达到峰值的时间更快，衰减速率比E - 4031敏感电流更慢。这些结果表明，Cs⁺和E - 4031抑制内向整流K⁺电流的不同成分，并且Cs⁺敏感电流对复极化的作用可以立即出现，并且在起搏电位范围内比E - 4031敏感电流更有效地持续。
