Hypoxia activates ATP‐dependent potassium channels in inspiratory neurones of neonatal mice
Hypoxia activates ATP‐dependent potassium channels in inspiratory neurones of neonatal mice
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缺氧激活新生小鼠吸气神经元中 ATP 依赖性钾通道
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
D. W. Richter
中科院分区：
文献类型：
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作者：
S. L. Mironov;K. Langohr;M. Haller;D. W. Richter
1 将新生小鼠（4至12天龄）的呼吸中枢分离在700μm厚的脑干切片中。在吸气神经元中分析了全细胞 K+ 电流和单个 ATP 依赖性钾 (KATP) 通道。 2 在细胞贴附斑块中，KATP 通道的电导为 75 pS，并显示内向整流。它们的门控是电压依赖性的，并且通道活性随着膜超极化而降低。使用含 Ca2+ 的移液器溶液测得的电导较低（1.5 mM Ca2+ 时为 50 pS），表明细胞外 Ca2+ 的强直抑制。 3 KATP 通道活性在缺氧期间可逆增强。从浴中除去氧气后 3-4 分钟达到最大效果。开放概率的缺氧增强是由于通道开放时间的增加和通道关闭时间的减少。 4 在由内而外的斑块和对称的 K+ 浓度中，通道电流在大约 0 mV 处反转。通道活性被 ATP (300-600 μM)、格列本脲 (10-70 μM) 和甲苯磺丁脲 (100-300 μM) 阻断。 5 在二氮嗪 (10-60 μM) 存在下，KATP 通道的活性在由内而外、由外而外和细胞贴附的斑块中均增加。在切除后保留在切片内的外向斑块中，KATP 通道的活性因缺氧而增强，这种效应可以通过内源性神经调节剂的释放来介导。 6 全细胞 K+ 电流 (IK) 在负膜电位下失活，这类似于 KATP 通道门控的电压依赖性。缺氧 3-4 分钟后，超极化和去极化膜电位的 K+ 电流均增加。 IK 被甲苯磺丁脲 (100-300 μM) 部分阻断，在其存在下，IK 的缺氧增强作用被消除。 7 我们得出结论，KATP 通道参与髓质呼吸活动的缺氧抑制。
1 The respiratory centre of neonatal mice (4 to 12 days old) was isolated in 700 μm thick brainstem slices. Whole‐cell K+ currents and single ATP‐dependent potassium (KATP) channels were analysed in inspiratory neurones. 2 In cell‐attached patches, KATP channels had a conductance of 75 pS and showed inward rectification. Their gating was voltage dependent and channel activity decreased with membrane hyperpolarization. Using Ca2+‐containing pipette solutions the measured conductance was lower (50 pS at 1.5 mM Ca2+), indicating tonic inhibition by extracellular Ca2+. 3 KATP channel activity was reversibly potentiated during hypoxia. Maximal effects were attained 3‐4 min after oxygen removal from the bath. Hypoxic potentiation of open probability was due to an increase in channel open times and a decrease in channel closed times. 4 In inside‐out patches and symmetrical K+ concentrations, channel currents reversed at about 0 mV. Channel activity was blocked by ATP (300‐600 μM), glibenclamide (10‐70 μM) and tolbutamide (100‐300 μM). 5 In the presence of diazoxide (10‐60 μM), the activity of KATP channels was increased both in inside‐out, outside‐out and cell‐attached patches. In outside‐out patches, that remained within the slice after excision, the activity of KATP channels was enhanced by hypoxia, an effect that could be mediated by a release of endogenous neuromodulators. 6 The whole‐cell K+ current (IK) was inactivated at negative membrane potentials, which resembled the voltage dependence of KATP channel gating. After 3‐4 min of hypoxia, K+ currents at both hyperpolarizing and depolarizing membrane potentials increased. IK was partially blocked by tolbutamide (100‐300 μM) and in its presence, hypoxic potentiation of IK was abolished. 7 We conclude that KATP channels are involved in the hypoxic depression of medullary respiratory activity.
影响因子：
56.9
作者：
SMITH, JC;ELLENBERGER, HH;FELDMAN, JL
通讯作者：
FELDMAN, JL
生命早期的缺氧和呼吸控制。
影响因子：
18.2
作者：
Haddad,GG;Mellins,RB
通讯作者：
Mellins,RB