Kupriyanov V V, Yang L, Deslauriers R
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba, Canada.
Am J Physiol. 1996 Apr;270(4 Pt 2):H1303-11. doi: 10.1152/ajpheart.1996.270.4.H1303.
The effect on intracellular Na+ ([Na+]i) and Rb+ fluxes if reduced [ATP]/ [ADP] and increased Pi has been investigated by 1 mM potassium cyanide (KCN) or KCl (control) infusion (24 min) in Langendorff perfused rat hearts. 87Rb, 23Na, or 31P nuclear magnetic resonance (NMR) spectra were acquired to measure intracellular Rb+ (a congener for K+, 20% substitution), Na+, and phosphates. KCN infusion (14-24 min) caused decreases in phosphocreatine (34 +/- 12% of initial), ATP (64 +/- 17), and Rb content (71 +/- 7) and increases in Pi (273 +/- 65) and [Na+]i (210 +/- 52). Dimethylamiloride (10 microM) did not change the rate of Na+ accumulation. The rate constant of unidirectional Rb+ efflux (min-1) increased during KCN treatment by 70% (0.061 +/- 0.006 vs. 0.036 +/- 0.004, P = 0.0001). KCN-stimulated Rb+ efflux was inhibited by glibenclamide (Glib, 10 microM. 0.042 +/- 0.009, P = 0.0001 vs. KCN) and alpha-cyano-4-hydroxycinnamate (0.5 mM, 0.047 +/- 0.008, P < 0.002 vs. KCN). KCN moderately decreased the Rb+ influx rate (to 82 +/- 17%, P = 0.01), which was depressed more significantly in the presence of Glib (47 +/- 17%, P = 0.03). We suggest that inhibition of Na(+)-K(+)-adenosinetriphosphatase (ATPase) by Pi is responsible for intracellular Na+ accumulation, whereas K+ loss is associated with both activation of ATP-sensitive K+ channels and the K(+)-lactate-cotransporter and inhibition of Na(+)-K(+)-ATPase.
通过向Langendorff灌注的大鼠心脏中注入1 mM氰化钾（KCN）或氯化钾（KCl，对照）24分钟，研究了降低的[ATP]/[ADP]和升高的无机磷酸盐（Pi）对细胞内钠离子浓度（[Na⁺]i）和铷离子通量的影响。采集了⁸⁷Rb、²³Na或³¹P核磁共振（NMR）光谱，以测量细胞内铷离子（钾离子的类似物，20%替代）、钠离子和磷酸盐。注入KCN（14 - 24分钟）导致磷酸肌酸（降至初始值的34 ± 12%）、ATP（降至64 ± 17）和铷含量（降至71 ± 7）降低，Pi（升至273 ± 65）和[Na⁺]i（升至210 ± 52）升高。二甲基氨氯吡脒（10 μM）未改变钠离子积累速率。在KCN处理期间，单向铷离子外流速率常数（分钟⁻¹）增加了70%（0.061 ± 0.006对比0.036 ± 0.004，P = 0.0001）。格列本脲（Glib，10 μM，0.042 ± 0.009，与KCN相比P = 0.0001）和α - 氰基 - 4 - 羟基肉桂酸（0.5 mM，0.047 ± 0.008，与KCN相比P < 0.002）抑制了KCN刺激的铷离子外流。KCN适度降低了铷离子内流速率（降至82 ± 17%，P = 0.01），在存在Glib的情况下下降更显著（降至47 ± 17%，P = 0.03）。我们认为Pi对钠钾腺苷三磷酸酶（ATP酶）的抑制作用导致细胞内钠离子积累，而钾离子流失与ATP敏感性钾通道的激活、钾离子 - 乳酸共转运体以及钠钾ATP酶的抑制均有关。
