title: Potassium channel activation, hyperpolarization, and vascular relaxation.
abstract: 1) Numerous compounds and changes in physical state functions shift the membrane potential of vascular smooth muscle to more negative values. The consequence is a vasodilatation because Ca2+ channels are closed. K+ channel opening frequently causes the hyperpolarization. 2) Acidification of the blood substitute solution, a fall in O2 partial pressure, and an increase in blood flow dilate arterial vessels. Acidosis is associated with a rise in K+ permeability and a simultaneous fall in Na+ permeability. Prostacyclin has a 20-30% share, and EDHF a 70-80% share in hypoxic vasodilatation. Experiments with iloprost (PGI2 analogue) confirmed the K+ channel opening properties of this drug. A voltage-dependent K+ channel and a Ca(2+)-activated K+ channel, via the influence of cA-PK or cG-PK, are responsible for the hyperpolarization with iloprost and with oxygen deficiency. 3) With 23Na+ nuclear magnetic resonance techniques, it has been demonstrated that with flow-dependent vasodilatation, proteoheparan sulphate integrated in the membrane of endothelial cells possibly served as a "flow sensor". With an external strain, such a compound can go from a randomly coiled state to an oriented state. Based on these viscoelastic properties, heparan sulphate proteoglycan is present as a random coil under "no flow" conditions and as an unfurled filament structure with increasing flow. This conformational change produces additional anionic binding sites to which Na+ ions of the blood are bound. A membrane hyperpolarization could be directly initiated by this Na+ binding via the protein fraction within the macromolecule or via a change in zeta-potential. Therefore, these ions can trigger the signal transduction for a vasodilatory vessel reaction. Decrease in flow is followed by a structural change of the macromolecule towards coil conformation, a release of Na+ ions and, thus, an interruption of the signal chain. 4) Cicletanine, aqueous garlic extract, and ajoene cause a concentration-dependent membrane hyperpolarization and are potent vasodilators. A cicletanine concentration, which is attained by the dosage given to patients, is sufficient to produce these effects. Under noradrenaline, the cicletanine effect is amplified. Aqueous garlic extract and ajoene exert a hyperpolarizing and vasodilating influence even in a concentration which may occur in the extracellular space by the administration of a single garlic clove. 5) The stationary activation curve "developed force vs. membrane potential" satisfactorily explains the effects of K+ channel openers. The tight electromechanical coupling expressed by this curve comprises a 50% vasorelaxation for a 2.5 mV hyperpolarization. In the linear part of the curve, the coupling ratio is 5.1 mV/g.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Institute of Physiology, Free University of Berlin, FRG.
authors.forename: G
authors.initials: G
authors.lastname: Siegel
authors.forename: A
authors.initials: A
authors.lastname: Walter
authors.forename: F
authors.initials: F
authors.lastname: Schnalke
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: E
authors.initials: E
authors.lastname: Buddecke
authors.forename: G
authors.initials: G
authors.lastname: Loirand
authors.forename: G
authors.initials: G
authors.lastname: Stock
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D046508:Culture Techniques; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D016285:Iloprost / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D015221:Potassium Channels; D011725:Pyridines; D015222:Sodium Channels; C038068:cicletanine; D019204:GTP-Binding Proteins; D016285:Iloprost; D002118:Calcium; D009638:Norepinephrine