Decreased 4-aminopyridine sensitive K+ currents in endothelial cells from hypertensive rats.
Endothelial cell function is altered in hypertension. The present study was performed to evaluate the alterations in K+ 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). Ca2+-dependent K+ channel blockers, charybdotoxin and apamin, a voltage-dependent K+ channel blocker, 4-aminopyridine, and a non-selective K+ channel blocker, tetrabutylammonium, were used to characterize K+ currents. Depolarizing command steps evoked delayed K+ outward currents in cells from both strains. The current density of 4-aminopyridine sensitive K+ currents was significantly smaller in SHR-SP than in WKY (1.5 +/- 0.4 vs. 4.9 +/- 0.6 pA/pF, at 36 mV, n = 13, p < 0.01), whereas that of other K+ 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, n = 54 vs. -33.5 +/- 1.4 mV, n = 50, p < 0.01). Depolarization by 4-aminopyridine, but not that by charybdotoxin+apamin, abolished the difference in membrane potentials between SHR-SP and WKY (n=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+ 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.
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D001030:Apamin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D051666:Kv1.5 Potassium Channel; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY; D020521:Stroke / Q000235:genetics
D004338:Drug Combinations; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018999:Charybdotoxin; D001030:Apamin; D015761:4-Aminopyridine