Biomaterial Database

Kinetics of the conductance evoked by noradrenaline, inositol trisphosphate or Ca2+ in guinea-pig isolated hepatocytes. 1990

D C Ogden, and T Capiod, and J W Walker, and D R Trentham

Department of Pharmacology, King's College London, Strand.

1. Guinea-pig hepatocytes respond to noradrenaline (NA, 5-10 microM) with a large membrane conductance increase to K+ and Cl-. The response has a long initial delay (range 2-30 s). Following the delay, the K+ conductance (studied in Cl(-)-free solutions) rises quickly to a peak in 1-2 s and is maintained in the continued presence of NA, though often with superimposed oscillations of conductance. The roles of intracellular Ca2+ and D-myo-inositol 1,4,5-trisphosphate (InsP3) in this complex response have been investigated by rapid photolytic release of intracellular Ca2+ (from Nitr5-Ca2+ buffers) or InsP3 from 'caged' InsP3. 2. A rapid increase of intracellular [Ca2+] produced an immediate membrane conductance increase which rose approximately exponentially to a new steady level, consistent with a direct activation of Ca2(+)-dependent ion channels. 3. Following a pulse of InsP3, conductance rose after a brief delay (range 70-1500 ms) which was shortest at high [InsP3] or if the initial cytosolic [Ca2+] had been raised above normal levels. The maximum conductance produced by InsP3 was similar in each cell to the peak recorded with NA and could be evoked by InsP3 concentrations of 0.5-1 microM. 4. The rates of rise of conductance increased with InsP3 concentration in the range 0.25-12.5 microM (range 10-90%, rise times 90-1000 ms), indicating that InsP3-evoked Ca2(+)-efflux from stores increases with InsP3 concentration in this range. 5. Photochemically released InsP3 and Ca2+ activate at physiological concentrations the same membrane conductances as NA. The results indicate that the long initial delay in NA action occurs prior to or during generation of InsP3. The mechanism of the delay and the subsequent apparently all-or-none conductance increase during NA action are discussed in terms of the high co-operativity in InsP3 and Ca2+ actions and an additional positive feedback step. 6. Evidence was found of a negative interaction between [Ca2+] and InsP3-evoked Ca2+ release. The time course of the recovery of InsP3-evoked Ca2+ release following a rise of cytosolic [Ca2+] suggests that this interaction may be important in regulating oscillatory responses of [Ca2+] during hormonal stimulation of guinea-pig hepatocytes.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010782	Photolysis	Chemical bond cleavage reactions resulting from absorption of radiant energy.	Photodegradation
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
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
D002712	Chlorides	Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.	Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential