Ganz M B, Nee J J, Isales C M, Barrett P Q
Department of Medicine, Case Western Reserve University, Cleveland Veterans Affairs Medical Center, Ohio 44106.
Am J Physiol. 1994 May;266(5 Pt 1):C1357-65. doi: 10.1152/ajpcell.1994.266.5.C1357.
Aldosterone secretion from the adrenal glomerulosa (AG) cells is inhibited by atrial natriuretic peptide (ANP). Inasmuch as alterations in K+ conductance can modulate aldosterone secretion, the effect of ANP on intracellular K+ homeostasis was investigated. Intracellular K+ concentration ([K+]i) of AG cells was assessed by spectrofluorometry using the K(+)-sensitive dye, K(+)-binding benzofuran isophthalate. The resting value of [K+]i in AG cells was determined to be 120 +/- 1.2 mM (n = 37) in a HCO3-free, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered medium. Exposure of AG cells to ANP led to a dose-dependent, transient decrease in [K+]i, from 21 +/- 3.2% (n = 7) at 100 pM to 31 +/- 2.3% at 1 microM (n = 7). In the continued presence of ANP, a rapid recovery to near basal values of [K+]i was attained within 90 s. Measurements of membrane voltage using the potential sensitive dye 1-3(-sulfonatopropyl)-4-[beta-(-(di-n-butylamino)-6-naphthyl)vinyl ]- pyridinium betaine documented an accompanying change in membrane potential. Pretreatment of AG cells with barium (0.5 mM), tetraethylammonium (0.1 mM), charybdotoxin (100 nM), or ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (0.5 mM) blunted the ANP-induced decrease in [K+]i. ANP-(7-23), the ANP-C-receptor selective agonist, which does not elevate guanosine 3',5'-cyclic monophosphate (cGMP) did not alter [K+]i in contrast to cGMP (50 microM), which did. We conclude that ANP via the activation of the ANP A receptor alters K+ homeostasis through a Ca(2+)-activatable K(+)-conductive pathway likely to be the maxi-K channel.
心房利钠肽(ANP)可抑制肾上腺球状带(AG)细胞分泌醛固酮。鉴于钾离子电导的改变可调节醛固酮分泌,因此研究了ANP对细胞内钾离子稳态的影响。使用钾离子敏感染料钾离子结合苯并呋喃间苯二甲酸通过荧光分光光度法评估AG细胞内的钾离子浓度([K⁺]i)。在无HCO₃、N-2-羟乙基哌嗪-N'-2-乙烷磺酸缓冲培养基中,AG细胞内[K⁺]i的静息值确定为120±1.2 mM(n = 37)。将AG细胞暴露于ANP会导致[K⁺]i呈剂量依赖性短暂降低,从100 pM时的21±3.2%(n = 7)降至1 μM时的31±2.3%(n = 7)。在持续存在ANP的情况下,90秒内[K⁺]i迅速恢复至接近基础值。使用电位敏感染料1-3(-磺丙基)-4-[β-(-(二正丁基氨基)-6-萘基)乙烯基]-吡啶鎓甜菜碱测量膜电压,记录了膜电位的伴随变化。用钡(0.5 mM)、四乙铵(0.1 mM)、蝎毒素(100 nM)或乙二醇双(β-氨基乙醚)-N,N,N',N'-四乙酸(0.5 mM)预处理AG细胞可减弱ANP诱导的[K⁺]i降低。ANP-(7-23),一种不升高鸟苷3',5'-环磷酸(cGMP)的ANP-C受体选择性激动剂,与能升高cGMP的cGMP(50 μM)不同,它不会改变[K⁺]i。我们得出结论,ANP通过激活ANP A受体,通过一条可能是大电导钙激活钾通道的钙激活钾离子传导途径改变钾离子稳态。