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Biomedical subjects

B Nilius

Publications and source records attributed to B Nilius.

At least 217 records · Page 12Linked to original sources
PubMed1986

Possible functional significance of a novel type of cardiac Ca channel.

Pacemaker activity of sino-atrial (SA) node cells is explained by reconstructing the pacemaker potentials using a Hodgkin-Huxley type model which based on voltage clamp data. The new point of the reconstruction is the consideration of kinetic data of a novel "transient" (T-type) Ca current. It is demonstrated that the diastolic depolarization is closely correlated to the activation of the T-type Ca current. Overshooting SA node action potentials, however, are evoked by activation of the conventional L-type Ca current triggered by a depolarization induced by the T-type Ca current.

Animals↗
PubMed1986

Properties of aconitine-modified sodium channels in single cells of mouse ventricular myocardium.

Effects of the plant alkaloid Aconitine on the kinetics of sodium channels were studied in enzymatically isolated single cells of the mouse ventricular myocardium. Aconitine (1 mumol/l) induced a prolongation of the 90% repolarization of action potentials from 52.4 +/- 3.7 ms to 217.0 +/- 12.5 ms. Delayed terminal repolarization and oscillatory afterpotentials preceded spontaneous activity with high frequencies. Peak sodium currents were diminished from 28.0 +/- 9.0 to 14.0 +/- 6.0 nA. The reversal potential of the sodium current was shifted from 16.0 +/- 11.0 to -8.0 +/- 6.0 mV (52.5 mmol/l extracellular sodium concentration) suggesting a decreased selectivity of the Aconitine-modified Na channels. The m-affinity-curves were shifted 31 mV towards more negative potentials at a constant slope. The h affinity-curves were shifted in the same direction by 13 mV. The slope parameter of the h affinity-voltage relationship was enlarged from 9.1 +/- 2.2 mV to 15.6 +/- 4.4 mV. Shifts in m affinity and h affinity resulted in an increased "window". The alkaloid modified channels inactivated extremely slowly at potentials negative to -40 mV, but showed a fast and complete inactivation at potentials positive to -40 mV.

Aconitine↗
PubMed1986

Calcium channel types in cardiac myocytes: modulation by dihydropyridines and beta-adrenergic stimulation.

We used the patch clamp technique to record unitary calcium (Ca2+) channel activity in freshly dissociated ventricular myocytes from adult guinea pigs. We found two types of Ca2+ channels with distinct permeation and gating properties and different sensitivity to pharmacological agents. One channel (T-type) requires negative membrane potentials to remove inactivation. It gives rise to a transient mean current and is not affected by dihydropyridines or isoproterenol. The other Ca2+ channel (L-type) has a larger unitary barium-conductance, activates at more positive potentials and its averaged current decays much more slowly. It shows a distinct gating pattern with different gating modes, the proportion of which is drastically altered by dihydropyridine Ca2+-channel agonists and antagonists. L-type channel activity is modulated by beta-adrenergic stimulation by a mechanism of action which differs from that of dihydropyridine Ca2+-channel agonists.

Animals↗
PubMed1986

Increased sensitivity of ventricular myocardium to intracellular calcium-overload in Syrian cardiomyopathic hamster.

Papillary muscles of Syrian hamsters with morphologically defined cardiomyopathy (CM), and of control hamsters (Co) have been studied electrophysiologically. Co and CM muscles differ significantly in the following electrophysiological parameters: resting potential (-79.8 +/- 2.9 mV in Co, -74.3 +/- 5.5 mV in CM), action potential duration at 25% repolarization (30.0 +/- 3.6 ms in Co, 25.1 +/- 2.7 ms in CM), and at 90% repolarization (120.0 +/- 21.9 ms in Co, 171.6 +/- 24.1 ms in CM), upstroke velocity of phase 0 depolarization (73.7 +/- 12.8 V/s in Co, 48.4 +/- 8.7 V/s in CM). When superfused with K+-free solutions Co muscles did not show any oscillatory after-potentials up to 15 mmol/l CaCl2. In contrast to this CM muscles respond to K+-free superfusion with oscillatory afterpotentials, transient spontaneous activity and dramatically reduced upstroke velocity. CM muscles respond much more sensitively to an intracellular Ca2+ overload than Co preparations.

Action Potentials↗
PubMed1985

Sodium current in single myocardial mouse cells.

Morphologically intact single myocardial cells of the adult mouse show a length of 132 +/- 20 microns, a width of 21 +/- 5 microns, and a height of 10 +/- 4 microns (all mean +/- SD) and are brick-like in shape. A one suction pipette method is used for voltage clamp of those single cells. The determined time constant of capacitive current tau = 35 +/- 14 microseconds is very short. Series resistance rs, membrane resistance rm, and membrane capacity Cm are calculated to be 192 +/- 48 k omega, 6.1 +/- 1.1 M omega, and 186 +/- 92 pF (all mean +/- SD), respectively. Assuming the specific unit membrane capacitance of 1 microF/cm2, a total membrane area of 1.86 X 10(-4) cm2 is determined yielding a specific membrane resistance Rm of 1,134 omega cm2. Settling time of voltage clamp is 30 microseconds. TTX-block of sodium current is described by 1:1 binding with a KD value of 1.4 X 10(-6) M. Using a reduced extracellular sodium concentration the maximum Na current is between 25 and 40 nA at voltages between -40 and -30 mV. Currents of between +20 and +30 mV reverse in an outward direction. Inward currents are approximated by a m3h model. The time constant of activation decreases from 0.7 ms at -60 mV to 0.12 ms at +20 mV. The time constant of inactivation falls from 9.1 ms at -60 mV to 0.6 ms at + 20 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Direct evidence of a Ca-sensitive inactivation of slow inward channels in frog atrial myocardium.

Electrical properties of frog atrial myocardium under Ca-free conditions (30 min superfusion with 1 mM EGTA) were examined using a microelectrode and voltage clamp technique. Action potentials recorded from atrial trabeculae were extremely prolonged, up to more than 2 s. The resting potential was shifted towards more positive values (-60 +/- 9 mV (Ca-free); -75 +/- 4 mV (control); n = 6). Slow inward currents inactivated extremely slow showing time constants between 2 and 3 s. The voltage-dependence of the time constant of inactivation was found to be U-shaped in Ca-containing but bell-shaped in Ca-free solutions. After a 30 min Ca-free superfusion, the surfaces of the atrial trabeculae studied by scanning electron microscopy changes from being rough to extremely smooth, supposedly indicating a change in the surface coat. Using electron-microprobe analysis within a surface layer of about 0.2 micron thickness direct measurements of the Ca concentration showed a reduction under Ca-free conditions by more than 200-fold. Electrophysiological measurements, morphological findings and measurements of the Ca concentration in the surface region directly suggest the existence of a Ca-sensitive inactivation of slow channels in frog atrial myocardium.

Action Potentials↗
PubMed1985

Use dependent depression of fast sodium current in heart muscle by the new antiarrhythmic substance Bonnecor (AWD 19-166, GS 015).

A new antiarrhythmic compound (Bonnecor AWD 19-166, GS 015) was studied in its effects on the fast sodium channel in two types of cardiac preparations (rabbit ventricular myocardium, frog atrial trabecules). AWD 19-166 depressed the maximum upstroke velocity of the action potentials in ventricular myocardium (50% inhibition at 5 X 10(-6) mol/l) and decreased the fast inward current in frog atrial myocardium. High frequent trains of pacing pulses produced a pacing dependent extra block of both the maximal upstroke velocity and the fast inward current. It is concluded that AWD 19-166 blocks the fast sodium channel in a use dependent manner.

Action Potentials↗
PubMed1985

Electrophysiological effects of a new antiarrhythmic substance Bonnecor (AWD 19-166, GS 015) on mammalian myocardium.

A new antiarrhythmic acting drug (Bonnecor, AWD 19-166, GS 015, 3- Carbethoxyamino-5-dimethyl-amino-acetyl-iminodibenzyl -hydrochloride) was tested electrophysiologically on isolated sinus node preparations and right ventricular papillary muscle of the rabbit. Transmembrane potentials were measured using a standard microelectrode technique. The substance was tested within a concentration range between 0.1 and 10 mg/l (2.5 X 10(-7) to 2.5 X 10(-5) mol/l). AWD 19-166 exerted negative chronotropic effects due to decreasing of the slope of the diastolic depolarization in sinus node cells. In ventricular myocardium AWD 19-166 increased the threshold strength of stimulation, prolonged the duration of action potentials at 90% but shortened it at 25% repolarization. The maximum upstroke velocity was found to be depressed. The maximum overshoot potential was diminished inspite of a drug-induced hyperpolarization of the resting transmembrane potential. Analysis of membrane responsiveness due to premature stimulation showed a concentration-dependent delay in the restitution of the maximum upstroke velocity of the premature action potentials and both a flattening and a shift towards more negative potentials of the potential-responsiveness relationship. AWD 19-166 decreased both the maximum upstroke velocity and the duration of Ca-mediated action potentials in concentrations between 2 and 8 mg/l. It is concluded that AWD 19-166 is able to exert potent antiarrhythmic effects in influencing both the fast and slow channel activity.

Action Potentials↗
PubMed1985

Inotropic effects of the antiarrhythmic compound Bonnecor (AWD 19-166, GS 015).

The inotropic effects of the new antiarrhythmic compound AWD 19-166 have been studied at constantly driven isolated left atria of guinea pig (weight between 250 and 350 g). AWD 19-166 exerted dose-dependently negative inotropic effects. Half maximum effects were measured at 1.7 mg/l (n = 7). At concentrations higher than 5 mg/l the negative inotropic effects were found to be irreversible.

Animals↗
PubMed1985

Electrical effects of the new antiarrhythmic compound Bonnecor (AWD 19-166, GS 015) under arrhythmogenic conditions.

Electrical effects of the new antiarrhythmic compound Bonnecor (AWD 19-166, GS 015) were studied under conditions known to increase the intracellular Ca2+ activity (extracellular K+-deprivation, application of glycosides). In K+ free solutions right ventricular papillary muscles showed an extreme acceleration of the initial repolarization indicating an intracellular Ca overload. AWD 19-166 could not prevent the initial shortening of action potentials and seems to be less effective in K+ free than in K+ containing solutions. In partially depolarized (22 mmol/lK+) right ventricular papillary muscles oscillatory afterdepolarizations were not suppressed by AWD 19-166. However, the compound prevented the generation of irregular action potentials triggered by the afterdepolarizations.

Action Potentials↗
PubMed1984

Temperature dependent properties of sodium inward current of frog atrial trabecles.

From frog atrial trabecles sodium inward current in dependence on temperature was investigated using a double sucrose gap technique. For a first period of cooling the Arrhenius plot of time constants of activation and inactivation and peak current time tp show a break near 5 degrees C that is not detectable for the data of the succeeding period of rewarming. For the second and third cooling period the extreme delay of currents failed indicating an irreversible change of membrane structure after a temperature cycle. Rewarming always causes hysteresis of tp whose genuiness is proven by comparison of currents of temperature jump and ramp.

Animals↗
PubMed1984

Stimulation of Ca-dependent action potentials in mammalian ventricular myocardium by a novel dihydropyridine.

Effects of the novel dihydropyridine compound BAY-K 8644 on Ca-dependent slow action potentials in guinea pig papillary muscles were studied. The maximum upstroke velocity Umax of slow action potentials (sAP) increased in concentrations between 2 X 10(-9) and 2 X 10(-7) mol/1 BAY-K whereas at higher concentrations Umax decreased again. Half maximum effects were obtained at 2.5 X 10(-8) mol/l (20 mol/L K+). The increase in Umax could be antagonized by nifedipine in a similar range of concentrations. The duration of sAP was changed depending on the pacing interval. At short pacing intervals (up to 2 s) sAP were abbreviated by BAY-K. BAY-K also induced a small hyperpolarization in 20 mmol/l K+ and lowered the threshold voltage distinctly. Washing out of BAY-K resulted always in an overshooting lengthening of sAP. BAY-K strongly increased Umax at 40 mmol/l K+. The relationship between Umax and the membrane potential was shifted to increased Umax values. At concentrations higher than 6 X 10(-7) mol/l BAY-K produced oscillatory afterdepolarizations indicating a drug-induced Ca overload. All the experimental findings are consistent with the hypothesis that the novel dihydropyridine compound BAY-K 8644 activates Ca-channels in the mammalian ventricular myocardium.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1984

Rabbit atrial myocardium in hypoxic conditions: rate dependent variation of contraction.

The dependence of contraction in the atrial myocardium on the stimulation pattern was studied in normoxic and hypoxic conditions. Isotonic contractions were measured from left atrial muscle strips of the rabbit. At rapid stimulation hypoxia produced a negative inotropic effect which disappeared at slower stimulation and became a positive inotropic one. The potentiation of a first beat after a pause in stimulation was enhanced by hypoxia because the contractions were stronger depressed at steady state than after a pause. At all pacing patterns the relative maximum rate of shortening and re-lengthening were independent of the oxygen-supply. After application of epinephrine in hypoxia they were enhanced and so was peak shortening. The findings suggest an impaired or altered function of the sarcolemma only under the degrees of hypoxia chosen.

Animals↗
PubMed1984

Electrophysiological effects of the tricyclic antidepressant desipramine on mammalian myocardium.

Effects of desipramine (DPr), a tricyclic antidepressant, on isolated trabeculae of the right rabbit atrial myocardium were studied using a standard microelectrode technique. Between 10(-7) and 10(-4) g/ml DPr reduced the maximum upstroke velocity Vmax of the action potentials. The membrane responsiveness was found to be depressed for DPr increased the time constant of the recovery of Vmax in a concentration-dependent manner distinctly. The voltage-Vmax relationships were shifted to more positive potentials and were flattend by increasing the concentration of DPr. DPr prolonged the duration of the action potentials on all levels of repolarization. Between 10(-7) and 10(-5) g/ml both resting and overshoot potential were found to be unchanged. At concentrations higher than 10(-5) g/ml slow response action potential insensitive to 10(-5) mol/l TTX were evoked, the resting transmembrane potential depolarized, spatial inhomogeneities in transmembrane potential and triggered activity could be observed. DPr may act antiarrhythmogenically in a quinidine-like manner at concentrations between 10(-7) and 10(-5) g/ml by (1) decreasing the fast channel conductance, (2) delaying the recovery of the fast channel. At concentrations higher than 10(-5) g/ml DPr could effect arrhythmogenic actions by a complete depression of fast response action potentials, unmasking of slow response action potentials and generation of severe spatial inhomogeneities.

Action Potentials↗
PubMed1984

Pacing-induced transient depolarizations in rabbit atrial myocardium.

Transient afterdepolarizations (TD) were analyzed following a train of paced action potentials in isolated pectinate muscles bordering the crista terminalis in rabbit right atria. After cessation of a rapid drive TD peaked between 400 and 700 ms. The amplitude of TD were found to be pacing-dependent (maximum at 250 ms pre-drive pacing interval 12.9 +/- 2.2 mV, n = 27). At pacing intervals longer than 1000 ms no TD could be observed but pacing intervals shorter than 250 ms provoked a triggered activity. Verapamil (13.2 X 10(-6) mol.1(-1) completely blocked pacing-induced TD. TD could be described quantitatively using a model of the transient inward current.

Animals↗
PubMed1984

Analysis of hyperpolarizing afterpotentials in the atrial myocardium.

Afterpotentials following a train of paced action potentials in isolated pectinate muscles bordering the crista terminalis in the rabbit atrial myocardium were analyzed. Electrical measurements were performed using a standard microelectrode technique. An ultrastructural stereological analysis was undertaken to study intercellular clefts within the preparations used. After cessation of a rapid drive, afterpotentials showed an initial depolarization followed by a delayed hyperpolarization. The initial depolarization could be blocked by verapamil (13.2 microM) leaving a monotonous hyperpolarization. This hyperpolarization was modelled supposing a K+-depletion out of morphological identified intercellular clefts. From best approximation of the measured after-hyperpolarization (1) the internal K+ activity was estimated to be in the range of 82 to 90 mM depending on the pacing interval Io. It decreased due to shortening of Io; (2) the accumulated "cleft" K+ activity was estimated to be about 2 mM at a pre-drive pacing interval of 250 ms; it decreased by increasing of Io, (3) decreasing of Io accelerated the K+-depletion, (4) a single beat accumulation of about 0.28 mM was estimated. The morphologically measured geometry of the intercellular clefts (mean cleft width 0.5 micron, ratio of cleft and cell volume 0.09 +/- 0.03) agreed well with the electrophysiological findings.

Action Potentials↗