Biomaterial Database

Modulation of the Ca2+ channel voltage sensor and excitation-contraction coupling by silver. 1992

T Oba, and M Yamaguchi, and S Wang, and J D Johnson

Department of Veterinary Anatomy and Cellular Biology, College of Veterinary Medicine, Ohio State University, Columbus 43210.

Ag+ (0.5-10 microM) is known to produce a transient contraction of intact frog skeletal muscle fibers followed by complete inhibition of excitation-contraction (E-C) coupling. We have carried out physiological and biochemical experiments to investigate the basis of this effect. Dihydropyridine (DHP) Ca2+ channel blockers, which inhibit the voltage sensor of the Ca2+ channel, completely inhibit Ag+ contractions. Removal of extracellular Ca2+, or blockade of Ca2+ entry with cadmium, does not inhibit Ag+ contractions. Activation of the Ca2+ channel's voltage sensor with the Ca2+ channel agonists Bay K 8644 or with perchlorate, potentiates the Ag(+)-induced contraction. Ag+ binds to the partially purified rabbit skeletal muscle Ca2+ channel and inhibits DHP binding (IC50 = 1.1 microM) and sulfhydryl (SH) reactivity (IC50 = 0.11 microM) over the concentration range where it inhibits E-C coupling. Oxidation of free SH groups by H2O2 or their reaction with DTNB prevents Ag+ contractions, while DTT reduction of oxidized SH groups restores Ag+ contractions. These results suggest that Ag+ binds to critical SH groups on the DHP receptor Ca2+ channel, resulting in modification of the channel's voltage sensor and the failure of E-C coupling.

UI	MeSH Term	Description	Entries
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009132	Muscles	Contractile tissue that produces movement in animals.	Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009543	Nifedipine	A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.	Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
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
D011896	Rana temporaria	A species of the family Ranidae occurring in a wide variety of habitats from within the Arctic Circle to South Africa, Australia, etc.	European Common Frog,Frog, Common European,Common European Frog,Common Frog, European,European Frog, Common,Frog, European Common
D004563	Electrochemistry	The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes.	Electrochemistries
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
D001703	Biophysics	The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.	Mechanobiology
D012834	Silver	An element with the atomic symbol Ag, atomic number 47, and atomic weight 107.87. It is a soft metal that is used medically in surgical instruments, dental prostheses, and alloys. Long-continued use of silver salts can lead to a form of poisoning known as ARGYRIA.
D013438	Sulfhydryl Compounds	Compounds containing the -SH radical.	Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl