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Biomedical subjects

M Morad

Publications and source records attributed to M Morad.

143 records · Page 8Linked to original sources
PubMed1976

Merocyanine 540 as an optical probe of transmembrane electrical activity in the heart.

Frog hearts stained with merocyanine 540 shows a 1.5 to 2.0 percent increase in fluorescence intensity at 585 nanometers during the cardiac action potential when excited with a 540-nonometer light beam. Fluorometric action potentials similar to those recorded with intracellular microelectrodes in pacemaker, atrial, and ventricular tissues were recorded by focusing a 1-millimeter excitation beam on various regions of the heart. The signal-to-noise ratio for a single action potential ranged between 10/1 and 40/1. In spontaneously pacing hearts the slower rate of rise of the fluorescence action potential is due to the slow propagation of the electrical signal. In solutions containing normal calcium concentrations the fluorometric signal is altered by contractions. Merocyanine 540 is biologically inert as it stains the cardiac cell membrane and acts as a sensitive optical probe of the change in transmembrane potential.

Action Potentials↗
PubMed1976

Extracellular potassium accumulation and inward-going potassium rectification in voltage clamped ventricular muscle.

Measurements of afterpotential, action potential duration, and output of a potassium-sensitive microelectrode indicate that the application of long clamp pulses (1 to 8 seconds) to frog ventricular muscle is accompanied by a change in the extracellular potassium concentration. The plot of the magnitude of the potassium accumulation against the clamped membrane potential yields an N-shaped relation similar to the "steady state" current-voltage relation. The accumulation studies confirm a strong inward-going (anomalous) potassium rectification.

Action Potentials↗
PubMed1976

Electromechanical properties of the single cell-layered heart of tunicate Boltenia ovifera (sea potato).

The tubular heart of the sea potato is composed of a single layer of myoepithelial cells interconnected near the extraluminal surface by specialized junctions. If these junctions are used as the border which separates the luminal from extraluminal membrane, the surface area ratio, luminal:extraluminal, is approximately 12:1. A single myofibril is located near the luminal surface in each cell. Current passed across the heart wall in the direction that depolarizes the luminal membrane and hyperpolarizes the extraluminal membrane immediately produces "all-or-none" action potentials and contractions. Current passed in the opposite direction fails to produce action potentials until after the break of the stimulus, suggesting anodal break excitation of the hyperpolarized luminal membrane. High potassium solutions depolarized the myoepithelium and produced contractions only when applied to the luminal surface of the heart. [Ca]0 increases and [Mg]0 decreases twitch tension only on the luminal surface of the heart. The transwall resistivity is low (50-100 omega/cm2) due to an extracellular shunt. Because of this shunt and the larger surface area of the luminal membrane, the extraluminal membrane is effectively clamped to the potential of the luminal membrane and is not capable of directly influencing excitation-contraction coupling. These findings suggest that only the luminal membrane of the sea potato myoepithelium is capable of generating an action potential and triggering contraction.

Action Potentials↗
PubMed1975

Electromechanical studies on the inotropic effects of acetylstrophanthidin in ventricular muscle.

Three phases in the inotropic response of acetyl strophanthidin (AcS) on the electromechnical activity of the frog ventricular myocardium were identified and studied using a single sucrose voltage-clamp technique and other conventional electrophysiological methods. 2. the positive inotropic response of the drug was accompanied by a shift in tension-voltage relation, so that more tension developed with every depolarization step above the mechanical threshold (-50mV). Only at higher drug concentrations or with long exposure times did the mechanical threshold shift to more negative membrane potentials (-60 to-70 mV). 3. In tetrodotoxin-treated muscles AcS produced marked potentiation of twitch tension and an appropriate shift in the tension-voltage relation. 4. the positive inotropic response of the drug was not related to the magnitude of the direction of the fast or slow Na current. 5. in tetrodotoxin-treated ventricular strips the direction or the magnitude of the secondary inward current (ICa or INa) were not related to the inotropic effect of AcS. 6. AcS shortens the action potential markedly during the later stages of its positive inotropic response. When Ca2+ is omitted from the bathing solution AcS not only fails to shorten the action potential, but often prolongs it. 7. The shortening of the action potential in the presence of AcS is accompanied by an increase in the "instantaneous" membrane conductance both at rest and during the time course of the plateau. 8. The decline in the positive inotropic response of the drug was accompanied by the shortening of the action potential. Electrical or chemical prolongation of the action potential restored the full positive inotropic response if the membrane had not depolarized. 9. Membrane depolarization and the development of diastolic tension always occurred at later stages of drug action. Elevation of [Mg+2]degrees to 5 or 10 mM prevented or suppressed the membrane depolarization and the diastolic tension. 10. KCl-induced contractures were potentiated throughout the duration of drug exposure. The tonic component of the contracture tension was markedly elevated especially at later stages of drug action. 11. The experimental evidence suggests that no unitary mechanism could account for multiple actions of acetyl strophanthidin. However, the contributions of the Na pump, the Ca+2 sequestering system, and the K-efflux system to the various stages of drug action are discussed.

Action Potentials↗
PubMed1974

Single cell layered heart: electromechanical properties of the heart of Boltenia ovifera.

The heart of Boltenia ovifera (the sea potato) is a tubular structure formed by a single layer of myocardial cells. Electron microscopic studies show that each cell contains a single myofibril located adjacent to the luminal surface of the cell. Electrical and mechanical measurement of a cannulated perfused heart demonstrate that only the luminal membrane is excitabble and elicits contraction on depolarization. Calcium and magnesium exert antagonistic effects on tension, and potassium depolarizes the myocardium and produces contractures when the luminal membrane is exposed to various concentrations of these ions. The extraluminl membrane does not respond electrically or mechanically to calcium magnesium or potassium, and its potential seems to be effectively "clamped" by the luminal membrane. Functionaly, therefore, this heart consists of a single active membrane with the adjacent contractile apparatus.

Action Potentials↗
PubMed1972

Relaxing effects of catecholamines on mammalian heart.

1. The effect of catecholamines on the time course and amplitude of contraction and on KCl-induced contractures has been studied in mammalian hearts.2. Marked and reproducible contractures could be obtained in mammalian ventricular trabeculae and papillary muscles after beta-adrenergic block with propanolol or if the hearts were depleted of their catecholamine stores by reserpine or by chemical denervation with 6-hydroxydopamine.3. In neonatal hearts with lower endogenous catecholamine stores and poorly developed sarcoplasmic reticulum KCl contractures are easily produced.4. Catecholamines potentiate twitch tension and relax the contracture tension under all of the above circumstances.5. The relaxant effect of catecholamines is present during the time course of a twitch. This increased relaxation rate as well as the shortening of the time-to-peak of tension is independent of the variation in the duration of the action potential.6. The shortened relaxation time is present when the action potential is shortened with anodal repolarization or prolonged with cathodal depolarization (voltage-clamp).7. The relaxant effect of catecholamines on the twitch is temperature and rate dependent. The effect is observed in the presence of high or low concentrations of calcium.8. The presence of catecholamines is necessary for full relaxation of mammalian heart muscle under high performance conditions or states of calcium overload.9. It is proposed that catecholamines exert their relaxant effect independent of their positive inotropic effect by stimulating the sequestering system (sarcoplasmic reticulum, mitochondria or sarcolemma) for calcium.

Action Potentials↗
PubMed1971

Excitation-concentration coupling in frog ventricle: evidence from voltage clamp studies.

1. Membrane potential, tension and membrane current were simultaneously recorded from frog ventricular strips in a modified sucrose-gap which enabled control of membrane potential by voltage clamp.2. Shortening the frog ventricular action potential by repolarizing the membrane to the resting potential terminates contraction.3. Depolarization to the level of the normal action potential plateau for longer than about 80-100 msec (up to 30 sec) produces and maintains tension for the duration of the depolarization.4. Depolarizations less than about 80 msec in duration generate no tension but can facilitate the tension response to subsequent depolarizations. The facilitating effect of a short depolarizing pulse persists for no longer than 0.5 sec.5. The mechanical threshold is about -50 mV; the relation between membrane potential and tension is fairly linear from about +5 to +80 mV.6. Variation of holding potential, below the mechanical threshold, has no effect on the tension-voltage relation. The absolute membrane potential rather than pulse amplitude determines the developed tension.7. Increasing external calcium increases the slope of the voltage-tension relation.8. Contraction of the frog ventricle is directly controlled by the electrical activity of the surface membrane.

Action Potentials↗
PubMed1969

Contracture and catecholamines in mammalian myocardium.

Contractures induced by KCl are produced in cat ventricular muscle after depletion of catecholamine stores by previous treatment with reserpine or by selective blocking of adrenergic receptor sites with propranalol. Contractures are reproducible for 2 to 3 hours and are markedly depressed by the addition of epinephrine. The relaxation of contracture induced by epinephrine parallels the eftect of this compound of shortening the duration of the normal twitch. The failure of the normal mammalian myocardium to maintain tension in solutions of high KCI concentration appears to be related to the endogenous amounts of catecholamines in the tissue.

Animals↗
PubMedDate not supplied

Rapid photochemical inactivation of Ca2+-antagonists shows that Ca2+ entry directly activates contraction in frog heart.

'Calcium-antagonists' are a group of pharmacological agents which are potent vasodilators and are clinically used for the treatment of angina. They are thought to block Ca2+ channels in vascular smooth muscle and myocardium but other sites of action have been proposed. These agents bind tightly to heart muscle and suppress action potential and contraction. Nifedipine and nisoldipine (BAY K 5552) are Ca2+ antagonists which have o-nitrobenzyl groups and are photolabile. We have found that short pulses of UV light rapidly inactivate these drugs in ventricular muscle. This observation allowed us to study the effect of Ca2+ antagonists on action potential, Ca2+ current and tension in conditions in which diffusion of those drugs from their site of action was not rate limiting. Our studies, described here, suggest that the primary mechanism of action of Ca2+ antagonists is the blockade of the Ca2+ channel and support the idea that extracellular space is the immediate source of contractile Ca2+ in the frog heart.

Action Potentials↗
PubMedDate not supplied

Cardiovascular safety of second-generation antihistamines.

Reports of serious cardiac arrhythmia associated with some second-generation antihistamines have prompted concern for their prescription. This article reviews the nature of the adverse events reported and concludes that the blockade of potassium channels, particularly the subtype responsible for the rapid component of the delayed rectifier current (IKr), is largely responsible for such adverse cardiac events. Consequently, antihistamines with little or no interaction with these channels are expected to have the greatest safety margin. The main cardiac arrhythmia of concern is that of torsades de pointes, a potentially fatal phenomenon characterized by prolonged ventricular depolarization that manifests as a prolonged QT interval and polymorphic ventricular tachycardia, with twisting of the QRS complexes. Based on pre-clinical and clinical evidence, it appears that loratadine, cetirizine, and fexofenadine are safe from cardiac arrhythmia via the IKr channel, whereas astemizole and terfenadine have a propensity to cause ventricular tachyarrhythmias.

Animals↗