Ca(2+)-dependent block and potentiation of L-type calcium current in guinea-pig ventricular myocytes. 1993

S E Bates, and A M Gurney
Department of Pharmacology, UMDS, St Thomas's Hospital, London.

1. The caged calcium compound nitr-5 has been used to investigate the response of the L-type calcium current (ICa) of guinea-pig ventricular cells to a rapid increase in the free intracellular calcium concentration ([Ca2+]i). 2. When 2 mM nitr-5 or 3 mM DM-nitrophen was loaded into cells via a patch pipette and photolysed during the decay phase of ICa, a partial block of the current developed within 75 ms. The block was reduced by increasing the pre-flash [Ca2+]i and enhanced by adding high concentrations of Ca2+ chelators to the pipette-filling solution. 3. The photolysis-induced block was not suppressed in the presence of isoprenaline, suggesting a direct action of Ca2+ on the channels rather than a mechanism involving channel phosphorylation. 4. The most prominent effect of nitr-5 photolysis was a slow potentiation of ICa. When ICa was activated at frequencies between 0.05 and 0.7 Hz with various levels of pre-flash [Ca2+]i, peak ICa was approximately doubled in amplitude following photolysis. 5. At a stimulation frequency of 0.05 Hz, when nitr-5 was the only chelator present in the pipette, the time course of the potentiation was fitted by a single exponential with a time constant (tau P) of 2.7 min. When 1 mM CaCl2 was added to the pipette-filling solution, the time course of the potentiation was slowed (tau P = 6 min), although its amplitude was unchanged. With 12 mM BAPTA (a calcium chelator) added instead of CaCl2, the response was accelerated (tau P = 1.7 min). 6. Equimolar substitution of extracellular Ca2+ with Ba2+ significantly suppressed the flash-induced potentiation. The time course of the potentiation of the barium current, IBa (tau P = 1.9 min) was similar to that of ICa with BAPTA in the pipette. Potentiation of IBa was largely blocked in Ca(2+)-depleted cells when CaCl2 was omitted from the pipette. 7. When ICa was activated at frequencies of > or = 0.1 Hz, with 1 mM CaCl2 added to the nitr-5 (2 mM) in the pipette, the onset of the flash-induced potentiation was best fitted by two exponentials; one was similar to the single component seen at 0.05 Hz and the other was approximately one order of magnitude faster. The contribution of the faster component was positively correlated to the stimulation frequency. 8. The flash-induced potentiation of ICa was suppressed in the presence of a supramaximal concentration of the beta-adrenergic agonist isoprenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D007424 Intracellular Fluid The fluid inside CELLS. Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297 Male Males
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010782 Photolysis Chemical bond cleavage reactions resulting from absorption of radiant energy. Photodegradation
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
D002614 Chelating Agents Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D004533 Egtazic Acid A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID. EGTA,Ethylene Glycol Tetraacetic Acid,EGATA,Egtazic Acid Disodium Salt,Egtazic Acid Potassium Salt,Egtazic Acid Sodium Salt,Ethylene Glycol Bis(2-aminoethyl ether)tetraacetic Acid,Ethylenebis(oxyethylenenitrile)tetraacetic Acid,GEDTA,Glycoletherdiamine-N,N,N',N'-tetraacetic Acid,Magnesium-EGTA,Tetrasodium EGTA,Acid, Egtazic,EGTA, Tetrasodium,Magnesium EGTA
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical

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