Decreased 4-Aminopyridine Sensitive K+ Currents in Endothelial Cells from Hypertensive Rats.
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<B>Endothelial cell function is altered in hypertension. The present study was performed to evaluate the alterations in K<SUP>+</SUP> channels in endothelial cells from hypertensive rats. Currents and membrane potentials were recorded in endothelial cells freshly dissociated from the aorta of stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto rats (WKY). Ca<SUP>2+</SUP> -dependent K<SUP>+</SUP> channel blockers, charybdotoxin and apamin, a voltage-dependent K<SUP>+</SUP> channel blocker, 4-aminopyridine, and a non-selective K<SUP>+</SUP> channel blocker, tetrabutylammonium, were used to characterize K<SUP>+</SUP> currents. Depolarizing command steps evoked delayed K<SUP>+</SUP> outward currents in cells from both strains. The current density of 4-aminopyridine sensitive K<SUP>+</SUP> currents was significantly smaller in SHR-SP than in WKY (1.5±0.4 <I>vs</I>. 4.9±0.6 pA/pF, at 36 mV, <I>n</I> =13, <I>p</I> <0.01), whereas that of other K<SUP>+</SUP> current components did not differ between strains. The resting membrane potential of cells was significantly less negative in SHR-SP than in WKY (-25.0±1.7, <I>n</I> =54 <I>vs</I>. -33.5±1.4 mV, <I>n</I> =50, <I>p</I> <0.01). Depolarization by 4-aminopyridine, but not that by charybdotoxin+apamin, abolished the difference in membrane potentials between SHR-SP and WKY (<I>n</I> =7-10 in each strain). Immunostaining of endothelial cells by anti-Kv1.5 antibody was decreased in SHR-SP compared to WKY. In summary, the 4-aminopyridine sensitive K<SUP>+</SUP> currents in aortic endothelial cells were decreased in SHR-SP, which could contribute to the membrane depolarization. Decreased expression of Kv1.5 in SHR-SP might be associated with this alteration. (<I>Hypertens Res</I> 2002; 25: 589-596)</B>
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日本高血圧学会 | 論文
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