title: Potassium channel activation in vascular smooth muscle.
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 and a fall in O2 partial pressure 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. Cicletanine 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. Ajoene exerts a hyperpolarizing and vasodilating influence even in a concentration which may occur in the extracellular space by the administration of a single garlic clove. 4. 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. 5. In the vascular smooth muscle, vasorelaxation can be evoked by membrane hyperpolarization which is linked to a simultaneous increase in K+ outward current and 42K+ efflux. In the case of substances whose influence is solely or partially receptor-mediated, cyclic nucleotides may be involved in vasorelaxation. Since cyclic nucleotides also hyperpolarize through an increase in K+ conductance, the resulting dilatation often cannot be divided into its single components. Therefore, it is sensible not to give the term "K+ channel opener" too fine a definition. The term should be applied to all substances and changes in physical states which predominantly increase the open probability of K+ channels finally via a conformational change in the cell membrane. For example, giving an acidic blood substitute solution (acidosis) is an intervention opening K+ channels. Which K+ channel and which single channel conductance is concerned in a particular case, and which 'mediator' may participate, become secondary questions.
authors.affiliation: Institute of Physiology, Free University of Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Siegel
authors.forename: J
authors.initials: J
authors.lastname: Emden
authors.forename: K
authors.initials: K
authors.lastname: Wenzel
authors.forename: J
authors.initials: J
authors.lastname: Mironneau
authors.forename: G
authors.initials: G
authors.lastname: Stock
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D016285:Iloprost / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D015221:Potassium Channels; D011725:Pyridines; D016627:Oxidopamine; C038068:cicletanine; D016285:Iloprost; D007213:Indomethacin