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E Coraboeuf

Publications and source records attributed to E Coraboeuf.

At least 37 records · Page 2Linked to original sources
PubMed1992

Pro-arrhythmic effect of nicorandil in isolated rabbit atria and its suppression by tolbutamide and quinidine.

Nicorandil, a potent vasodilator substance which exerts its effects through complex mechanisms including KATP channel activation, has so far been reported to exert antiarrhythmic but not pro-arrhythmic cardiac activity. We now examined the effects of 10(-4) M nicorandil on spontaneously active or electrically driven isolated rabbit atria. Nicorandil (a) significantly reduced the action potential duration at both 50% (by approximately 45%) and 80% (by approximately 30%) repolarization and the effective refractory period (by approximately 25%) and (b) reproducibly induced short periods of tachycardia either in normal Tyrode solution after a single extra-stimulus or in low-potassium media in the absence of extra-stimulation. Quinidine (10(-5) M) or the KATP channel inhibitor, tolbutamide (10(-5) M), suppressed the nicorandil-induced arrhythmias. It is suggested that the pro-arrhythmic effect of nicorandil results from its KATP channel opener activity and occurs essentially when the underlying conditions facilitate re-entry.

Action Potentials↗
PubMed1992

Effects of atrionatriuretic factor on Ca2+ current and Cai-independent transient outward K+ current in human atrial cells.

The effect of 10 nM atrial natriuretic peptide (ANF) on macroscopic L-type calcium current, ICa, and calcium-independent outward potassium current, Ilo, were studied in myocytes isolated from human atrial trabeculae using the whole-cell-recording patch-clamp technique. When cells were dialysed with pipette media containing 0.2 mM GTP, ANF reduced ICa by 37.81% +/- 5.4% at +20 mV and Ilo by 21.72% +/- 3.68% at +60 mV in a reversible manner. When ICa was increased by beta-adrenoreceptor stimulation (0.1 microM isoproterenol) or by the phosphodiesterase inhibitor isobutylmethylxanthine (10 microM) ANF reduced ICa by 24.99 +/- 3.4% and by 39.9 +/- 6.3% respectively. In cells dialysed with GTP-free pipette media, ANF increased ICa markedly (39.8% +/- 7%) and reversibly, whereas it still depressed Ilo (18.92% +/- 2%). Addition of 0.2 mM GTP[gamma S] to the pipette solution in the absence of GTP increased ICa, decreased Ilo and suppressed the effect of ANF on both ICa and Ilo. It is suggested that activation of the ANF receptor in human atrial cells reduces ICa via guanylate-cyclase-dependent cGMP production, increases ICa via Gs protein activation and decreases Ilo via Gi protein activation.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Large-conductance chloride channels of new-born rat cardiac myocytes are activated by hypotonic media.

Large-conductance chloride (LC-type Cl-) channel activity was studied in rat ventricular myocyte membrane during development. In contrast with results previously obtained in cultured ventricular myocytes of the new-born rat, we failed to record single-channel activity in freshly isolated myocytes whatever the age of the animal (from 2 days old to adult) and the recording patch configuration used. However, spontaneous single-channel activity of LC-type Cl- channels was recorded in bleb membranes of myocytes of rats younger than 12 days, with a higher frequency in excised inside-out membrane patches than in cell-attached membrane patches. In intact neonatal myocytes, application of hypotonic media (150 mOsm) also initiated the channel activity, after variable delays (25-200 s). The channel could not be activated by suction applied through the pipette and was not observable in cells from rats older than 15 days. The LC-type Cl- channels showed properties similar to those reported in other preparations and previously observed in cardiac cultured cells: they had a large single-channel conductance of 400 pS in symmetrical 150 mM NaCl, showed multiple subconductance states, a relatively high selectivity to Cl- ions over Na+ ions (PCl/PNa = 24.6), were blocked by 10 microM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and showed voltage-dependent inactivation. They were not activated by 10 microM colchicine or 3 microM cytochalasin D.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

The calcium antagonist D600 inhibits calcium-independent transient outward current in isolated rat ventricular myocytes.

1. The whole-cell voltage-clamp technique was applied to isolated rat ventricular myocytes to investigate the effects of D600 (10(-9)-10(-3) M) on the intracellular calcium-independent component of transient outward current. I(lo), recorded in a sodium-free medium containing 0.5 x 10(-3) M-cadmium and 10(-6) M-ryanodine. 2. Externally applied D600 reduced Ilo in a dose-dependent, reversible manner, and accelerated the decay of the current. 3. Current-voltage relationships and corresponding activation curves (determined assuming I(lo) to be a pure potassium current) were shifted towards positive potentials in the presence of 10(-3) M but not 10(-5) M-D600. Steady-state inactivation curves were not affected by either low or high concentrations of D600. 4. Under control conditions, the inactivation of I(lo) is composed of a fast and a slow component. The amplitude of the slow component was more strongly reduced by D600 than that of the fast one. In the presence of 10(-3) M-D600, the slow component was entirely suppressed. 5. Both the time to peak Ilo and the time constant of the fast component of inactivation were markedly reduced at all potentials by D600. The time constant of the slow component was less sensitive to the drug. 6. When the relative quantity of charge carried by each kinetic component of Ilo was plotted versus the concentration of D600, the data could be fitted by two distinctly separate dose-response curves with an almost 100-fold difference between the two apparent dissociation constants, of which the values were 2.88 x 10(-6) M for the slow phase of inactivation and 2.07 x 10(-4) M for the fast one, with Hill coefficients of 0.68 and 0.73 respectively. 7. The inhibition of I(lo) by D600 displayed little or no use dependence, one of the major characteristics of the effects of phenylalkylamines on the cardiac calcium current ICa. 8. Our results show that at least part of I(lo) is sensitive to D600 in the same range of concentrations as ICa. Although the effects of D600 on the two currents differ in several points, this observation raises the possibility that, besides clear differences, certain similarities may exist between the channels responsible for I(lo) and ICa.

Animals↗
PubMed1991

Calcium current depression in isolated human atrial myocytes after cessation of chronic treatment with calcium antagonists.

The present study investigates the possibility that the slow calcium current of human atrial cardiac cells is modified by chronic treatment (1-24 months) with calcium antagonists (nifedipine, nicardipine, or diltiazem) in a manner different from a simple drug-induced blocking effect. Data from treated patients were recorded approximately 30 hours after cessation of the treatment and were compared with those of nontreated patients. In the treated group, the action potential plateau of atrial fibers was always markedly and irreversibly depressed, and action potential duration measured at 50% repolarization was markedly shortened (81 +/- 12 msec, n = 13) compared with normal values (155 +/- 9 msec, n = 28). In isolated atrial cells, peak calcium current density at +10 mV in treated cells was more than three times as small as that in nontreated cells. Steady-state inactivation relations of calcium current as a function of membrane potential were not significantly different in treated and nontreated cells. In contrast, in treated and nontreated cells superfused with 10(-6) M nifedipine, the curves were markedly shifted toward negative potentials. Cell superfusion with 10(-6) M Bay K 8644 increased calcium current to a larger extent in nontreated cells (sixfold increase) than in treated cells (threefold increase), whereas a 23-fold increase was observed in nontreated cells in which the current had been previously depressed by superfusion with 10(-6) M nifedipine. In contrast to Bay K 8644, 10(-7) M isoproterenol and 10(-8) M angiotensin II increased the calcium current to the same extent in both treated and nontreated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Effect of 2,3-butanedione 2-monoxime on slow inward and transient outward currents in rat ventricular myocytes.

The effect of 2,3-butanedione 2-monoxime (BDM), a substance possessing phosphatase-like activity, was studied on action potentials of isolated rat heart and on the slow inward calcium current and outward current (including the 4-aminopyridine (4-AP)-sensitive transient outward component), in rat ventricular myocytes. In contrast to what was observed by other authors in different species and cardiac tissues, BDM increased markedly the amplitude and duration of the rat ventricular action potential plateau. On the other hand, in the presence of 4-AP and ryanodine BDM shortened action potential duration. BDM decreased in a dose dependent manner the amplitude of both the slow inward calcium current and the transient outward current, accelerated their inactivation and shifted their steady-state inactivation-voltage relationships towards negative potentials. BDM also depressed other components of outward current. It is suggested that the lengthening effect of BDM on action potential duration results mainly from the simultaneous reduction of both the slow inward calcium current and the transient outward current, two antagonistic currents with unequal influences on action potential plateau development. The similarity of effect of BDM on these two currents also suggests that ionic channels generating them might require similar phosphorylation for their functioning.

4-Aminopyridine↗
PubMed1990

Effect of maitotoxin on calcium current and background inward current in isolated ventricular rat myocytes.

Maitotoxin (MTX) irreversibly suppressed the voltage-dependent calcium current after a variable delay, an effect which was preceded, in 61% of the cells, by a transient increase in calcium current partly attributable to a shift (4-7 mV) of the activation curve towards negative potentials. MTX also induced the development of a voltage-independent background inward current which did not occur in the absence of external calcium and was reduced by removal of external sodium, by calcium channel blockers and by high concentrations of quinidine. MTX-induced single channel activity consisted of long lasting bursts of inward current. Channel activity was voltage-independent, with a unitary conductance of 14 pS and an extrapolated reversal potential of +16 mV. Single-channel current amplitude was not detectably reduced in the absence of external calcium but strongly reduced in the absence of external sodium, in the presence of 2 mM nickel or when external sodium was replaced by 96 mM calcium or 50 mM barium. The channel activity was also inhibited by quinidine. It is concluded that MTX alters, then suppresses the voltage-activated calcium current and induces the development of a voltage-independent inward current, part of which results from the opening of nickel-sensitive cation channels, mostly permeable to sodium ions.

Animals↗
PubMed1990

Stimulatory effect of ouabain on T- and L-type calcium currents in guinea pig cardiac myocytes.

The effect of 10(-6) M ouabain on macroscopic low-threshold T-type Ca2+ and high-threshold L-type Ca2+ currents was studied by whole cell recording in isolated guinea pig ventricular myocytes superfused with K-free, Na-free media, i.e., after suppression of Na-K-ATPase activity and Na influx through the Na-Ca exchanger. Under such conditions, the amplitudes of the two currents were significantly increased by ouabain. In particular, the current occurring in the -50 to -20 mV range (T-type Ca2+) was increased two- to threefold by ouabain and suppressed by 40 microM Ni2+. Ouabain shifted by approximately 10 mV toward negative potentials the steady-state inactivation curve of the T-type Ca2+ current but not that of the L-type Ca2+ current. It is concluded that ouabain enhances not only L-type Ca2+ current but also T-type Ca2+ current possibly through different mechanisms.

Animals↗
PubMed1989

Barium- and calcium-permeable channels open at negative membrane potentials in rat ventricular myocytes.

Ca2+- and Ba2+-permeable channel activity from adult rat ventricular myocytes, spontaneously appeared in the three single-channel recording configurations: cell-attached, and excised inside-out or outside-out membrane patches. Single-channel activity was recorded at steady-state applied membrane potentials including the entire range of physiologic values, and displayed no "rundown" in excised patches. This activity occurred in irregular bursts separated by quiescent periods of 5 to 20 min in cell-attached membrane patches, whereas in excised patch experiments, this period was reduced to 2 to 10 min. During activity, a variety of kinetic behaviors could be observed with more or less complex gating patterns. Three conductance levels: 22, 45 and 78 pS were routinely observed in the same excised membrane patch, sometimes combining to give a larger level. These channels were significantly permeable to divalent cations and showed little or no permeability to potassium or sodium ions. The inorganic blockers of voltage-gated Ca channels, cobalt (2 mM), cadmium (0.5 mM) or nickel (3 mM), had no apparent effect on these spontaneous unitary currents carried by barium ions. Under 10(5) M Bay K 8644 or nitrendipine, the activity was clearly increased in about half of the tested excised inside-out membrane patches. Both dihydropyridines enhanced openings of the larger conductance level, which was only very occasionally seen under control conditions. When the single-channel activity became sustained under 5 x 10(-6) M Bay K 8644, it was possible to calculate the mean unitary current at different membrane potentials and show that the mean current value increased with membrane potential.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Electrical activity of human atrial fibres at frequencies corresponding to atrial flutter.

Little information is available about rate dependent changes in electrical activity of human myocardial cells. We therefore studied, in vitro, the electrical activity of adult human atrial fibres driven at frequencies near that of atrial flutter by means of the standard microelectrode technique. Thirty two atrial samples exhibiting "normal" responses with fast upstroke were selected. At very high frequencies, the action potential (AP) upstroke arose from the repolarisation phase of the preceding AP in spite of marked frequency induced shortening of the plateau. As the stimulation rate was progressively increased, the take off potential (TOP) was less and less negative and the maximal rate of depolarisation (Vmax) decreased. Moreover, in most preparations, a clear alternation between two types of action potentials occurred. Calcium channel inhibitors cobalt (5 mM) or diltiazem (5 x 10(-6) M) shortened AP duration, increased Vmax and markedly reduced alternation. Sodium channel inhibitors, tetrodotoxin (7.5 10(-6) M) or lignocaine (10(-5) M) shortened AP duration and induced a transient increase in Vmax. Ouabain (10(-6) M) prolonged AP duration, decreased Vmax, enhanced alternation and finally suppressed the 1:1 capture of the atrial tissue. Our results show that, at high driving rates corresponding to the frequencies of atrial flutter, slight variations in action potential duration induced by drugs are associated with marked concomitant variations in Vmax and probably with consequent modifications of the conduction velocity.

Action Potentials↗
PubMed1989

Effects of activation of ATP-sensitive K+ channels in mammalian ventricular myocytes.

A cromakalim analogue, SR 44866, is shown to open ATP-sensitive K+ channels in ventricular myocytes. The channels opened by SR 44866 were closed by internal ATP and had the same current-voltage relationship as ATP-sensitive K+ channels; channels closed by ATP could be opened by SR 44866. SR 44866 was effective when applied to either side of excised membrane patches and when included in the pipette during cell-attached membrane recordings. SR 44866 also opened channels in cell-attached membrane patches when it was applied to the cell membrane outside of the pipette. The current evoked by SR 44866 in whole cell recordings was inhibited by tolbutamide. SR 44866 reduced the duration of action potentials and the amplitude and duration of evoked muscle contractions in guinea pig papillary muscle, with dissociation constants of 6.8 microM at 24 degrees C and 1.9 microM at 34 degrees C and Hill coefficients of 1.72 and 1.71, respectively. We conclude that the opening of ATP-sensitive K+ channels has profound inhibitory effects on the electrical and mechanical activity of cardiac muscle.

Action Potentials↗
PubMed1988

Effect of 3-5-3'triiodothyronine treatment on cardiac action potential of streptozotocin-induced diabetic rat.

Electrical activity of rat atrium of streptozotocin-diabetic and control rats was compared. (i) As occurs in the ventricle, diabetes lengthens the cardiac atrial action potential. (ii) Treatment by T3 of diabetic animals decreases action potential duration to normal values and causes partial recovery in plateau decay during the late phase of repolarization. (iii) T3 treatment however, does not completely normalized the action potential of the diabetic rat atrium, which remains abnormal during the early phase of repolarization. These results demonstrate that some defects in membrane mechanisms involved in the early phase of action potential repolarization are attributable solely to diabetes. The possible nature of these mechanisms is discussed.

Action Potentials↗
PubMed1988

Comparative effects of three class I antiarrhythmic drugs on plateau and pacemaker currents of sheep cardiac Purkinje fibres.

The electrophysiological effects of three class I antiarrhythmic drugs, lignocaine, disopyramide, and penticainide, were compared in sheep cardiac Purkinje fibres. Action potential duration was shortened with all three drugs, the effect being small with disopyramide, moderate with penticainide, and greatest with lignocaine. Slowing down of the early phase of repolarisation was greatest with disopyramide, smaller with penticainide, and did not occur with lignocaine. Automaticity recorded in low potassium media was unaltered (disopyramide), depressed (penticainide), or stopped (lignocaine). Ionic currents were recorded in short fibres using the two microelectrode voltage clamp technique. The tetrodotoxin sensitive slow component of the sodium current was suppressed (lignocaine) or reduced (penticainide and disopyramide) and the instantaneous background potassium current slightly reduced (disopyramide more than penticainide), unaffected, or slightly increased (lignocaine). The three drugs depressed moderately and similarly the slow inward calcium current. The amplitude of the 4-aminopyridine sensitive transient outward potassium current was almost unaffected (lignocaine) or appreciably depressed (disopyramide more than penticainide). The pacemaker current was reduced greatly by lignocaine, moderately by penticainide, and slightly by disopyramide. Changes in ionic currents may explain the effects of the three drugs on action potential plateau and automaticity of sheep Purkinje fibres. It is concluded that the pronounced differences observed in the effects of these three class I antiarrhythmic drugs on pacemaker depolarisation and on initial repolarisation may justify a more discriminative subdivision of class I antiarrhythmic drugs.

Action Potentials↗
PubMed1987

Single chloride-permeable channels of large conductance in cultured cardiac cells of new-born rats.

Large conductance channels were observed in the membrane of cultured cardiac cells of newborn rats studied with the patch-clamp technique in cell-attached and inside-out configurations. These channels were observed in approximately equal to 4% of the patches. In the cell-attached configuration they exhibited outward rectification and partial inactivation. In the inside-out configuration no rectification occurred but inactivation was present, mainly during hyperpolarizations. Two channels with large single unit conductances (400-450 pS) and one with a smaller conductance (200-250 pS) were frequently observed in the same patch. The two large channels generally had different kinetics. Under steady-state conditions the opening probability of the faster channel appeared to be voltage-independent. The slower channel was activated by depolarization. In asymmetrical solutions the permeability ratios PNa/PCl were 0.03 and 0.24 for the larger and smaller channels, respectively; corresponding values for PBa/PCl were 0.04 and 0.09. It is proposed that in cardiac membranes the chloride permeability system is composed of widely dispersed microclusters forming grouped channels of different types and sizes.

Animals↗
PubMed1987

Abnormal pacemaking is modulated by sarcoplasmic reticulum in partially-depolarized myocardium from dilated right atria in humans.

Fifty human atrial specimens removed at time of cardiac surgery were studied in vitro. Thirty-four samples were selected as presenting partial cell depolarization and exhibiting slow response action potentials. Twenty of these preparations were automatic whereas 14 were not. Neither mean maximum diastolic potential (-52.8 +/- 1.3 mV and -49.3 +/- 2.2 mV respectively) nor maximum rate of depolarization (Vmax) (1.1 +/- 0.1 V/s and 1.3 +/- 0.8 V/s) significantly differed between these two groups. Abnormal automaticity due to phase 4 depolarization occurred in 12/13 preparations dissected from markedly dilated atria whereas it occurred in only 2/10 preparations sampled from non-dilated atria. A statistically significant relationship between in vitro abnormal pacemaking and atrial dilatations was found. We investigated the effects on abnormal pacemaker depolarization and automaticity of a reduction in the extracellular Na and Ca and of sarcoplasmic reticulum (SR) inhibitors. Abnormal pacemaker depolarization appeared to be much more sensitive to a reduction in the extracellular Na than in the extracellular Ca. Both Sr and Mg slowed the automatic rate. Ryanodine 3 X 10(-6) M, a specific SR inhibitor, irreversibly lengthened the spontaneous basic cycle duration to about 300% of control. Epinephrine up to 10(-4) M was ineffective in accelerating the residual spontaneous rhythm that persists after ryanodine action, although epinephrine markedly enhanced the overshoot and Vmax of the slow responses. It is concluded that, in the human atrial myocardium, abnormal pacemaking that develops at low level of membrane potential: is promoted by chamber dilatation; is strongly modulated by SR-dependent processes.

Adolescent↗
PubMed1987

Two types of transient outward currents in adult human atrial cells.

It has been suggested in a previous article [Escande et al., Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H843-H850, 1985] that transient outward currents may participate in the initial repolarization of human atrial fibers. The present study substantiates the existence of such currents in human myocardium. Membrane currents were recorded in enzymatically dissociated cells using the whole cell patch-clamp technique. Two kinds of transient outward currents were observed: 1) a long-lasting outward current, (ilo), which was suppressed by 4-aminopyridine. The time to peak of ilo was 18.0 +/- 0.7 ms, and its inactivation time constant was 35.7 +/- 2.1 ms at room temperature (test pulses, +20 mV; holding potential, -40 mV); 2) a brief outward current (ibo), which persisted with 3 mM 4-aminopyridine and exhibited a shorter time to peak (5.5 +/- 0.2 ms) and a faster decay (time constant, 9.1 +/- 1.8 ms). ilo was inhibited by Ba but was insensitive to the calcium blocker Co. Co blocked both the slow inward current (isi) and ibo. It is concluded that two different transient outward currents control the repolarization in human atrial cells.

4-Aminopyridine↗
PubMed1986

Characteristics of the time-dependent slow inward current in adult human atrial single myocytes.

The slow inward current isi plays a prominent role in impulse formation and slow conduction in the human heart. For this reason, it may be involved in a great variety of arrhythmias that occur clinically, particularly at the supraventricular level. isi also appears to be the major target of numerous cardioactive drugs daily administered to many patients. Difficulties encountered in voltage clamping human tissues, inevitably dissected from restricted zones of myocardium with inadequate geometry, may explain why direct measurements of this current have never been performed on multicellular human preparations. The recent development of enzymatic techniques allowing the isolation of calcium-tolerant myocytes has provided a solution to these problems. To our knowledge only one abstract has presented until now records of isi in human ventricular myocytes. We describe here the result of experiments carried out to investigate the slow inward current in single cells isolated from adult human atria. The present work provides the first quantitative description of this current in human myocytes.

Atrial Function↗