Levcromakalim causes indirect endothelial hyperpolarization via a myo-endothelial pathway.
1. Effects of K+ channel opener, levcromakalim, on vascular endothelial cells were examined. Under voltage- and current-clamp conditions, application of acetylcholine to dispersed endothelial cells isolated from rabbit superior mesenteric artery (dispersed RMAECs) produced hyperpolarization and outward currents. On the other hand, dispersed RMAECs did not respond to levcromakalim. 2. When membrane potential was recorded from endothelium in a mesenteric arterial segment, exposure to levcromakalim in a concentration range of 0.1 to 3 microM caused concentration-dependent hyperpolarization. The hyperpolarization was observed in the absence of external Ca2+ and was inhibited by 10 microM glibenclamide. 3. The presence of 1 mM heptanol did not affect the levcromakalin-induced hyperpolarization, whereas treatment of the mesenteric arterial segment with 20 microM 18 beta-glycyrrhetinic acid significantly reduced the hyperpolarization. The response to acetylcholine of RMAECs in an arterial segment with 18 beta-glycyrrhetinic acid was, however, similar to that without 18 beta-glycyrrhetinic acid. 4. These suggest that although RMAECs themselves are functionally insensitive to levcromakalim, those in an arterial segment are hyperpolarized by levcromakalim via myo-endothelial electrical communication.
Murai
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya 467-8603, Japan.
Muraki
K
K
Imaizumi
Y
Y
Watanabe
M
M
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D006034:Glycyrrhetinic Acid