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M Mazzanti

Publications and source records attributed to M Mazzanti.

48 records · Page 3Linked to original sources
PubMed1989

Intracellular Ca modulates K-inward rectification in cardiac myocytes.

In cardiac myocytes, instantaneous inward rectification of the K-rectifying channel is abolished by removal of divalent cations from the intracellular environment and can be restored by addition of Mg ions at submillimolar concentrations, which has led to the proposal that Mg ions regulate inward rectification in these cells (Matsuda et al., 1987; Vandenberg, 1987; Matsuda, 1988). Here we report that Ca, too, reduces outward current flow through single inward rectifier channels in cell-free inside-out patches at much lower (submicromolar) concentrations. Intracellular Ca induces rectification by decreasing the probability of the main open channel state and by favouring the opening of channel substrates. Ca concentrations generating rectification are in the range of the Ca transient during activity, suggesting that Ca ions can contribute to K-rectification during cardiac muscle contraction.

Animals↗
PubMed1988

K channel kinetics during the spontaneous heart beat in embryonic chick ventricle cells.

By averaging the current that passes through cell-attached patches on beating heart cells, while measuring action potentials with a whole-cell electrode, we were able to study K channels during beating. In 7-d chick ventricle in 1.3 mM K physiological solutions at room temperature, delayed-rectifier channels have three linear conductance states: 60, 30, and 15 pS. The 60 and 15 pS conductances can exist alone, but all three states may appear in the same patch as interconverting conductance levels. The delayed-rectifier conductance states have low densities (less than 10 channels per 10-microns diam cell), and all have a reversal potential near -75 mV and the same average kinetics. Outward K current through delayed-rectifier channels follows the upstroke without appreciable delay and lasts throughout the action potential. No inward current flows through delayed-rectifier channels during beating. The early outward channel has a nonlinear conductance of 18-9 pS depending on the potential. It also turns on immediately after the upstroke of the action potential and lasts on average only 50 ms. The early outward channel has an extrapolated reversal potential near -30 mV; no inward current flows during beating. The inward-rectifier has an extrapolated conductance and reversal potential of 2-3 pS and -80 mV in 1.3 mM K. Channel kinetics are independent of external K between 10 and 120 mM, and the channel conducts current only during the late repolarization and diastolic phases of the action potential. No outward current flows through inward-rectifier channels during beating. This work parallels a previous study of Na channels using similar techniques (Mazzanti, M., and L. J. DeFelice. 1987, Biophys. J. 52:95-100).

Action Potentials↗
PubMed1987

Na channel kinetics during the spontaneous heart beat in embryonic chick ventricle cells.

Using cell-attached and whole-cell recording techniques simultaneously allows the measurement of Na currents during action potentials in beating heart cells. In 7-d chick ventricle, the dynamic reversal potential for Na is 30 mV, which is 20 mV less than the reversal potential in nonbeating cells. This result implies that the spontaneous activity of heart cells raises the Na concentration at the internal face of the membrane to nearly 40 mM. Fitting the Na action currents to the Hodgkin and Huxley equations shows that patches may contain from 50 to 700 Na channels, with an average density of 23 +/- 21 per micron2. Only approximately 2% of the available Na channels are open at the peak of the Na action current. This low probability is a consequence of the channels' continual inactivation during the diastolic depolarization phase.

Action Potentials↗
PubMed1987

Regulation of the Na-conducting Ca channel during the cardiac action potential.

This paper describes the kinetics of an Na-conducting channel during spontaneous action potentials in beating heart cells and during simulated action potentials driven from the patch when the cell is not beating. Since the channel conducts Na only in Ca concentrations below 10(-6) M, and since it is insensitive to tetrodotoxin and has a conductance of 100 pS in 133 mM Na, we identify it as the Ca channel conducting Na in zero Ca. By comparing the channel in beating and nonbeating cells, but under conditions in which it experiences the same voltage in both cases, we observe that: open-channel conductance is the same in beating and nonbeating cells; the channel reversal potential is 25 mV in beating cells and 50 mV in nonbeating cells; the average current peaks later in beating cells than in nonbeating cells, and it has a different time course in the two cases that is not explained by the shift in reversal potential alone; and the average Na current through Ca channels in beating cells peaks much later during the action potential than we would expect if the channel were carrying Ca. We conclude that when the Ca channel conducts Na, its kinetics and reversal potential are strongly influenced by cytoplasmic factors that accompany beating, and that its behavior is not governed by voltage alone. We also conclude that when the Ca channel conducts Na, not only are its reversal potential and conductance altered from what they would be were the channel carrying Ca, but also the channel's kinetics depend on the permeant ion. Since only the channels in the patch are in zero Ca and are conducting Na, while the Ca channels surrounding the patch are in 1.5 mM Ca and are conducting Ca, our data support the idea that it is only the Ca passing through individual channels that influences the kinetics of those same channels.

Action Potentials↗
PubMed1987

[Treatment of recurrent supraventricular tachyarrhythmias with flecainide or a flecainide and amiodarone combination].

The acute electrophysiologic effects and therapeutic efficacy of intravenous and oral flecainide were assessed in 18 patients with recurrent supraventricular tachyarrhythmias, resistant to conventional antiarrhythmic agents. They were 22 to 76 years old (mean 50). Twelve patients underwent electrophysiologic study for the investigation of tachyarrhythmias. Of the whole four patients had functional longitudinal AH dissociation (dual AV pathways). These patients had provocable intra-AV nodal reentrant tachycardia (Group I). Six patients had a direct accessory AV pathway, that showed bidirectional conduction in 5 and retrograde conduction alone in 1 (Group II). These patients had provocable atrioventricular reentrant tachycardia using the accessory pathway as the retrograde limb of the tachycardia circuit. Two patients suffered from automatic supraventricular tachycardia (Group III). Group IV included patients with paroxysmal atrial flutter or fibrillation. The patients of this group did not discontinue chronic treatment with amiodarone. After baseline electrophysiologic evaluation, intravenous flecainide (2 mg/Kg body weight over 5 minutes) was given to patients of I and II group during induced reentrant tachycardia. Flecainide was administered to other patients during spontaneous episodes of tachyarrhythmias. Flecainide resulted in tachycardia termination in all patients of group I and in 4 patients of group II (66%). Tachycardia termination was due to block in the retrograde limb of the circuit. Before termination tachycardia cycle length increased significantly, mainly as the result of an increase in ventriculo-atrial conduction time. After intravenous flecainide therapy, reentrant SVT was non inducible in the patients of group I and in 4 patients of group II. Flecainide was successful in the acute termination of 100% of automatic supraventricular tachycardia and 75% of fibrillation. The patients with atrial flutter developed a faster ventricular rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node.

Individual cells were isolated from the sino-atrial node area of the rabbit heart using an enzyme medium containing collagenase and elastase. After enzymatic treatment the cells were placed in normal Tyrode solution, where beating resumed in a fraction of them. Isolated cells were studied in the whole cell configuration. Action potentials as well as membrane currents under voltage-clamp conditions were similar to those in multicellular preparations. Pulses to voltages more negative than about -50 mV caused activation of the hyperpolarizing-activated current, if. Investigation of the properties of this current was carried out under conditions that limited the influence of other current systems during voltage clamp. The if current activation range usually extended approximately from -50 to -100 mV, but varied from cell to cell. In several cases, pulsing to the region of -40 mV elicited a sizeable if. Both current activation and deactivation during voltage steps had S-shaped time courses. A high variability was however observed in the sigmoidal behaviour of if kinetics. Plots of the fully-activated current-voltage (I-V) relation in different extracellular Na and K concentrations showed that both ions carry the current if. While changes in the external Na concentration caused the current I-V relation to undergo simple shifts along the voltage axis, changes in extracellular K concentration were also associated with changes in its slope. Again, a large variability was observed in the increase of I-V slope on raising the external K concentration. The current if was strongly depressed by Cs, and the block induced by 5 mM-Cs was markedly voltage dependent. Adrenaline (1-5 microM) and noradrenaline (1 microM) increased the current if around the half-activation voltage range and accelerated its activation at more negative voltages. Often, however, drug application failed to elicit any modification of if. Current run-down was observed in nearly all cells, although at a highly variable rate. It was accelerated by raising the extracellular K concentration but did not show a marked use dependence. Both the if activation curve and the fully activated I-V relation were affected by run-down, the former being shifted to more negative values along the voltage axis and the latter being depressed with no apparent change of the if reversal potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Mechanical transients initiated by ramp stretch and release to Po in frog muscle fibers.

Single fibers from the tibialis muscle of Rana temporaria were subjected to ramp stretches during tetanic stimulation at a sarcomere length of approximately 2 microns. Immediately after the stretch, or after different time delays, the active fiber was released against a constant force equal to the isometric force (Po) exerted immediately before the stretch. Four phases were detected after release: an elastic recoil of the fiber's undamped elements, a transient rapid shortening, a marked reduction in the velocity of shortening (often to 0), and an apparently steady shortening (sometimes absent). Increasing the amplitude of the stretch from approximately 2 to 10% of the fiber rest length led to an increase in phase 2 shortening from approximately 5 to 10 nm per half-sarcomere. Phase 2 shortening increased further (up to 14 nm per half-sarcomere) if a time interval of 5-10 ms was left between the end of large ramp stretches and release to Po. After 50- to 100-ms time intervals, shortening occurred in two steps of approximately 5 nm per half-sarcomere each. These findings suggest that phase 2 is due to charging, during and after the stretch, of a damped element, which can then shorten against Po in at least two steps of approximately 5 nm/half sarcomere each.

Animals↗
PubMed1985

Storage and release of mechanical energy by active muscle: a non-elastic mechanism?

In frog muscle fibres, tetanically stimulated at a sarcomere length of about 2 micron, stretched at a velocity of 1 lengths-1 and released against a force equal to the maximum isometric, P0, a phase of rapid isotonic shortening takes place after release. As the amplitude of the stretch is increased from 1.5 to 9% of the initial length: (1) the amount of rapid isotonic shortening increases up to 9-10 nm per half sarcomere and (2) the stiffness of the fibre (an indication of the number of bridges attached) decreases to a value about equal to that measured during an isometric contraction. If a 5-10 ms delay is left between the end of stretch and release, the amount of rapid isotonic shortening increases to about 12 nm hs-1. A 300-500 ms delay, however, results in a decrease in rapid isotonic shortening to about 5 nm hs-1 and also results in a velocity transients against P0 that are similar to those described during release from a state of isometric contraction. It is concluded that the force attained after large, fast stretches is due to a greater force developed by each bridge and not to a greater number of bridges. After the elastic recoil (when the force is suddenly reduced to P0), these strained bridges are able to shorten by about 12 nm hs-1, suggesting that, during and immediately after stretching, they are charged to levels of potential energy greater than those attained in an isometric contraction.

Animals↗
PubMedDate not supplied

Fast technetium 99m-labeled sestamibi gated single-photon emission computed tomography for evaluation of myocardial function.

BACKGROUND: This study assesses the feasibility of 99mTc-labeled sestamibi electrocardiographic gated single-photon emission computed tomography (SPECT) with a short acquisition time (6.7 minutes, "fast" gated SPECT) for the evaluation of stress myocardial perfusion and poststress myocardial function. Simultaneous assessment of stress perfusion and poststress function is possible with standard gated SPECT acquisition (19.3 minutes) of stress-injected sestamibi. Sestamibi gated SPECT can be used to evaluate regional wall motion (RWM), thickening, and left ventricular ejection fraction (LVEF); the feasibility of fast gated SPECT has not been evaluated previously. METHODS AND RESULTS: Fifty patients were studied who underwent treadmill exercise, sestamibi injection (25 to 30 mCi), and standard gated SPECT 15 minutes after exercise, immediately followed by fast gated SPECT. All patients underwent rest 201Tl SPECT before exercise testing. All studies were analyzed by semiquantitative visual scoring. Both standard and fast gated SPECT were read for stress perfusion and poststress wall motion and thickening, dividing the left ventricle into 20 segments, on a 5-point scale described previously. The measurement of LVEF used a previously described automatic algorithm. Average myocardial counts per pixel were 58 +/- 19 for standard gated SPECT and 13 +/- 4 for fast gated SPECT (p = 0.0001). Heart/lung ratio was 10.2 +/- 4.8 for regular gated SPECT and 10.3 +/- 5.7 for fast gated SPECT (difference not significant). Perfusion analysis showed exact agreement in 92% of the segments (kappa = 0.76; p < 0.01). Correlation between LVEFs measured from standard and fast gated SPECT was 0.94. Analysis of 998 segments (two segments were uninterpretable) showed exact agreement in 96% (kappa = 0.89; p < 0.001) for RWM and 94% (kappa = 0.83; p < 0.001) for thickening between standard and fast gated SPECT. In 225 segments with abnormal RWM and 189 segments with abnormal thickening by both standard and fast gated SPECT, exact agreements were 0.92 for RWM (kappa = 0.90; p < 0.001) and 0.87 for thickening (kappa = 0.80; p < 0.01). CONCLUSIONS: Our data demonstrate that fast sestamibi gated SPECT is feasible and yields results equivalent to those of standard sestamibi gated SPECT with respect to left ventricular regional and global function.

Aged↗
PubMedDate not supplied

Solid-state and solution structure of lanthanide complexes of a new nonadentate tripodal ligand containing phenanthroline binding units.

The new nonadentate tripodal ligand trenphen (tris[(1,10-phenanthroline-2-carboxamido)-ethyl]amine) has been synthesized by condensation of tren [tris(2-aminoethyl)amine] with an excess of 1,10-phenanthroline-2-carboxylic acyl chloride. The ligand trenphen and its lanthanide complexes (Sm, Nd, Eu, Tb, and Lu) have been structurally characterized by single-crystal X-ray diffractometry. Crystals of trenphen.H2O.CH3CN, 1, are monoclinic, space group P2(1)/n, a = 14.9923(8) A, b = 17.4451(10) A, c = 17.1880(10) A, beta = 114.8290(10) degrees, V = 4079.9(4) A3, Z = 4. The solid-state crystal structures of the isostructural [Ln(trenphen)](OTf)3.yH2O.xEt2O.zCH3CN (OTf = CF3SO3) (Ln = Nd, y = 0.5, x = 1, z = 3 (2); Ln = Sm, y = 0.5, x = 1, z = 3 (3); Ln = Eu, y = 0.5, z = 3 (4); Ln = Tb, y = 0.5, x = 1, z = 1.5 (5); Ln = Lu, y = 0.5, x = 1, z = 1.5 (6)) (trigonal, P-3, Z = 2) show that the covalent tripod trenphen undergoes a rearrangement in the presence of lanthanide ions yielding three tridentate binding units which encapsulate the nine-coordinated lanthanide ion with a slightly distorted, tricapped, trigonal prismatic coordination geometry. The correlation observed between the decrease of Ln-N distances and the metal ionic radius indicates that trenphen, although containing rigid bidentate phenanthroline units, is sufficiently flexible to self-organize without steric constraints around lanthanide ions of different size. Solution-state NMR studies show that complexes 2-6 exist in acetonitrile solution as discrete rigid C3-symmetric species retaining the triple-helical structure observed in the solid state. NMR and ES-MS titration show the formation of bimetallic and trimetallic species in the presence of an excess of metal, whereas mononuclear bistrenphen complexes are obtained in the presence of an excess of ligand.

Journal Article↗
PubMedDate not supplied

[Exposure to wood dust in a group of carpentry craftsmen in secondary wood processing].

In order to evaluate the risk connected with wood dust exposure in millwork on a group of 13 craft industries, 74 area dust samplings and 74 personal dust samplings were made. In personal samplings both the total portion and the respirable fraction were calculated. Area samplings showed dust levels (average, standard deviation, fiducial limit, FLS95%) under ACGIH TLV-TWA for soft wood dust: TLV-TWA for hard wood was basically reached, and OTL levels gave evidence for high risk of exceeding TLV-TWA in the medium-long term. The exposure levels by personal samplings (average, standard deviation, fiducial limit, FLS95%) were clearly over TLV-TWA, both for hard woods and, although less clear, for soft woods. OTL levels gave evidence for a frankly unacceptable exposure condition in the medium-long term. Differences between average levels of total dust exposure (2.5 mg/m3) and respirable portion (2.3 mg/m3) were not statistically significant (p > 0.05) as well as the differences among the 4 groups of companies with homogeneous product activity (p > 0.05). In consideration of toxicological peculiarity of wood dust and carcinogenicity of wood manufacture as exposure circumstances classified in group 1 by IARC, the results show the need for prevention measures to reduce workers' exposure risk, by means of environmental improvement and better work organization, technological structures, individual attitudes and personal protection.

Air Pollutants, Occupational↗