Biomaterial Database

Ketamine inhibition of large conductance Ca(2+)-activated K+ channels is modulated by intracellular Ca2+. 1994

D D Denson, and D C Eaton

Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30322.

The present investigation was conducted to study the relationship between intracellular Ca2+ and inhibition of large conductance Ca(2+)-activated K+ (BK) currents by ketamine using excised patches from GH3 cells. Five ketamine concentrations were studied in the presence of six Ca2+ concentrations. The half-maximal inhibition for BK channel block by ketamine was increased from 4.1 +/- 0.7 microM at 0.1 microM intracellular Ca2+ to 230 +/- 74 microM at 100 microM intracellular Ca2+. Open probability (Po), Ca2+ concentration, and ketamine concentration data were best described by a competitive inhibition model. The inhibition constant for ketamine was 20.5 +/- 5.2 microM, and the Michaelis-Menten constant (Km) value for Ca2+ was 3.58 +/- 0.49 microM, which was not different from Km for Ca2+ in the absence of ketamine (3.33 +/- 0.37 microM). Taken alone, these data would suggest that Ca2+ and ketamine were competing for the same site on the channel protein. However, examination of open and closed interval data from patches containing only one channel show that ketamine primarily produces a decrease in the frequency of long-lived open events, suggesting that the effect of ketamine on BK channels may not be by a direct effect on channel proteins.

UI	MeSH Term	Description	Entries
D007425	Intracellular Membranes	Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.	Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D007649	Ketamine	A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.	2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
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
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D015221	Potassium Channels	Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.	Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel
D026902	Potassium Channel Blockers	A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.	Channel Blockers, Potassium,Potassium Channel Blocker,Blocker, Potassium Channel,Blockers, Potassium Channel,Channel Blocker, Potassium