title: EDHF is not K+ but may be due to spread of current from the endothelium in guinea pig arterioles.
abstract: Endothelium-derived hyperpolarizing factor (EDHF)-attributed hyperpolarizations and relaxations were recorded simultaneously from submucosal arterioles of guinea pigs with the use of intracellular microelectrodes and a video-based system, respectively. Membrane currents were recorded from electrically short segments of arterioles under single-electrode voltage clamp. Substance P evoked an outward current with a current-voltage relationship that was well described by the Goldman-Hodgkin-Katz equation for a K+ current, consistent with the involvement of intermediate- and small-conductance Ca2+-activated K+ channels. 1-Ethyl-2-benzimidazolinone relaxed the arterioles and evoked hyperpolarizations that were blocked by charybdotoxin, but not by iberiotoxin. Application of K+ induced depolarization under conditions in which EDHF evoked hyperpolarization. The Ba2+-sensitive component of the K+-induced current was inwardly rectifying, in contrast to the outwardly rectifying current evoked by substance P. EDHF-attributed hyperpolarizations in dye-identified smooth muscle cells were indistinguishable from those recorded from dye-identified endothelial cells in the same arterioles. These results provide evidence that EDHF is not K+ but may involve electrotonic spread of hyperpolarization from the endothelial cells to the smooth muscle cells.
authors.affiliation: Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia. h.coleman@med.monash.edu.au
authors.forename: H A
authors.initials: HA
authors.lastname: Coleman
authors.forename: M
authors.initials: M
authors.lastname: Tare
authors.forename: H C
authors.initials: HC
authors.lastname: Parkington
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D001464:Barium / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001685:Biological Factors / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000098:blood supply; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D001562:Benzimidazoles; D001685:Biological Factors; D002120:Calcium Channel Agonists; D004791:Enzyme Inhibitors; D010455:Peptides; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001464:Barium; D013373:Substance P; C064719:iberiotoxin; C102635:1-ethyl-2-benzimidazolinone; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium