Pácha J, Frindt G, Antonian L, Silver R B, Palmer L G
Department of Physiology and Biophysics, Cornell University Medical College, New York 10021.
J Gen Physiol. 1993 Jul;102(1):25-42. doi: 10.1085/jgp.102.1.25.
The activity of apical membrane Na channels in the rat cortical collecting tubule was studied during manipulation of the animals' mineralocorticoid status in vivo using a low-Na diet or the diuretic furosemide. Tubules were isolated and split open to expose the luminal membrane surface. Induction of Na channel activity was studied in cell-attached patches of the split tubules. No activity was observed with control animals on a normal diet. Channel activity could be induced by putting the animals on the low-Na diet for at least 48 h. The mean number of open channels per patch (NPo) was maximal after 1 wk on low Na. Channels were also induced within 3 h after injection of furosemide (20 mg/kg body wt per d). NPo was maximal 48 h after the first injection. In both cases, increases in NPo were primarily due to increases in the number of channels per patch (N) at a constant open probability (Po). With salt depletion or furosemide injection NPo is a saturable function of aldosterone concentration with half-maximal activity at approximately 8 nM. When animals were salt repleted after 1-2 wk of salt depletion, both plasma aldosterone and NPo fell markedly within 6 h. NPo continued to decrease over the next 14 h, while plasma aldosterone rebounded partially. Channel activity may be dissociated from aldosterone concentrations under conditions of salt repletion.
利用低钠饮食或利尿剂速尿在体内改变大鼠盐皮质激素状态的过程中,对大鼠皮质集合管顶端膜钠通道的活性进行了研究。分离出肾小管并将其剖开以暴露管腔膜表面。在剖开的肾小管的细胞贴附式膜片上研究钠通道活性的诱导情况。正常饮食的对照动物未观察到活性。将动物置于低钠饮食至少48小时可诱导通道活性。低钠饮食1周后,每个膜片的平均开放通道数(NPo)最大。注射速尿(20mg/kg体重/天)后3小时内也可诱导通道活性。首次注射后48小时NPo最大。在这两种情况下,NPo的增加主要是由于每个膜片的通道数量(N)增加,而开放概率(Po)保持恒定。随着盐耗竭或注射速尿,NPo是醛固酮浓度的饱和函数,在约8nM时活性达到半最大。在1-2周的盐耗竭后使动物补充盐分,血浆醛固酮和NPo在6小时内均显著下降。在接下来的14小时内NPo继续下降,而血浆醛固酮部分反弹。在补充盐分的情况下,通道活性可能与醛固酮浓度无关。