Competitive blocking of apical sodium channels in epithelia. 1983

E Frehland, and T Hoshiko, and S Machlup

Apical sodium-selective channels in frog skin, when blocked by amiloride or triamterene, exhibit fluctuations in current, the spectra of which are Lorentzian. These effects have been modeled previously with two-state and three-state models by Lindemann and Van Driessche. A recent observation by Hoshiko and Van Driessche that corner frequencies are lowered by increasing the apical sodium concentration cannot be accounted for by these models. We explore the possibility that sodium (S) and amiloride (A) compete for a site at the mouth of the channel. A new three-state channel model (sodium-occupied, open/unoccupied, open/amiloride-blocked) is analyzed. Its corner frequency is of the form fc = fco [1 + (A/KA)/(1 + S/KS)], consistent with the observed sodium dependence of the corner frequency. The minimum frequency, fco, and the inhibition constants, KA and KS, are expressed in terms of the rate constants of the model. To account for sodium self-inhibition, we postulate that two sodium ions in the channel may result in clogging--a fourth state. The two corner frequencies are calculated; so are the plateau values of the noise power. The noise power shows a maximum as a function of blocker concentration, as observed previously using triamterene. The four-state model predicts the observed suppression by small amounts of blocker of the low-frequency sodium (clogging) noise.

UI MeSH Term Description Entries
D007473 Ion Channels Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS. Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008433 Mathematics The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Mathematic
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011719 Pyrazines A heterocyclic aromatic organic compound with the chemical formula C4H4N2. Pyrazine
D011892 Rana catesbeiana A species of the family Ranidae (true frogs). The only anuran properly referred to by the common name "bullfrog", it is the largest native anuran in North America. Bullfrog,Bullfrogs,Rana catesbeianas,catesbeiana, Rana
D004848 Epithelium The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body. Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D000584 Amiloride A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705) Amidal,Amiduret Trom,Amiloberag,Amiloride Hydrochloride,Amiloride Hydrochloride, Anhydrous,Kaluril,Midamor,Midoride,Modamide,Anhydrous Amiloride Hydrochloride,Hydrochloride, Amiloride,Hydrochloride, Anhydrous Amiloride,Trom, Amiduret
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.

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