Search PubMed⌕ Search

Biomedical subjects

E Marban

Publications and source records attributed to E Marban.

139 records · Page 8Linked to original sources
PubMed1982

Effects of nystatin-mediated intracellular ion substitution on membrane currents in calf purkinje fibres.

1. Calf cardiac Purkinje fibres were exposed briefly to the ionophore nystatin to promote exchange of caesium for intracellular potassium. The effects of Cs loading were stable for at least 30 min, but they could be reversed by nystatin-mediated K loading.2. After Cs loading, the resting potential shifted to about -20 mV and the current-voltage relationship showed a strong inhibition of inwardly rectifying K channels.3. Anodal break stimulation evoked normal action potential upstrokes and twitch contractions. The early repolarization (phase 1) was markedly slowed.4. Cs loading simplified the pattern of current changes evoked by step depolarizations over the plateau range. Membrane current reached an inward peak and then declined monotonically.5. The current signal showed no hint of the transient outward current found in untreated or K-loaded preparations. Furthermore, Cs loading abolished the outward tails associated with deactivation of transient outward current, and occluded the blocking effect of the K-channel inhibitor 4-aminopyridine.6. Inhibition of transient outward current revealed a maximal inward current of about 5 muA/muF in 5.4 mM-Ca(o), which is considerably larger than the net inward current without Cs loading.7. The inward current was attributed to Ca channels on the basis of its sensitivity to membrane potential, extracellular Ca, D600, Mn and Cd.8. Cs loading also reduced slow current changes associated with delayed rectification and pace-maker depolarization.9. The results support the hypothesis that the transient outward current is carried by K(+) ions, while providing a method for unmasking inward Ca current.

Action Potentials↗
PubMed1982

Enhancement of calcium current during digitalis inotropy in mammalian heart: positive feed-back regulation by intracellular calcium?

1. Effects of digitalis compounds on slow inward Ca current I(si)) and contractile force were examined in ferret ventricular muscle (single sucrose-gap voltage clamp) and calf Purkinje fibres (two micro-electrode voltage clamp).2. In ventricular muscle, ouabain increased I(si) and inward current tails associated with I(si) conductance. The enhancement of I(si) followed a time course similar to the development of the positive inotropic effect, and it could be observed in the absence of aftercontractions or other signs of toxicit.3. The response of myocardial I(si) and twitch force to ouabain depended strongly on a previous history of driven action potentials.4. Veratridine, a toxin that promotes Na entry through tetrodotoxin-sensitive channels, also increased I(si) and twitch force in driven ventricular muscle preparations.5. The effects of ouabain, action potential stimulation and veratridine are consistent with reported effects of K-poor solutions in indicating that elevation of intracellular Na can lead to enhancement of I(si). Additional experiments suggest that the link between Na(i) and I(si) involves intracellular Ca.6. When Cs-loaded Purkinje fibres were bathed in solutions containing Sr instead of Ca, enhancement of I(si) by strophanthidin was abolished even though a positive inotropic response persisted.7. After intracellular injection of Purkinje fibres with EGTA, I(si) no longer increased with strophanthidin, although it remained responsive to adrenaline.8. Clear-cut increases in I(si) were seen in Cs-loaded Purkinje fibres even at very low concentrations of strophanthidin (20-50 nM), where the occurence of Na pump inhibition has been questioned.9. Positive regulation of Ca entry by intracellular Ca may act as a facilitory mechanism that amplifies myocardial responsiveness to digitalis and other inotropic interventions. Through changes in I(si), small rises in diastolic free Ca might lead to large increases in the activator Ca transient during contraction.

Animals↗
PubMed1980

Free calcium in heart muscle at rest and during contraction measured with Ca2+ -sensitive microelectrodes.

Direct measurements of free Ca2+ in heart cells are needed for an understanding of the regulation of contractility. We developed and used Ca2+ -sensitive microelectrodes with fine tips, stable properties and ample sensitivity to free Ca2+ in the sub-micromolar range. In quiescent ventricular muscle, measurements which passed tests for electrode sealing and cell viability gave a mean free Ca2+ concentration of 0.26 microM. During contractures, we recorded Ca2+ transients rising as high as 10 microM. In studying the effects of catecholamines on free Ca2+ and force, we found evidence that adrenaline can reduce myofibrillar Ca2+ sensitivity in intact heart muscle.

Animals↗
PubMedDate not supplied

Cell-type specificity of preconditioning in an in vitro model.

We investigated whether preconditioning could protect several cultured cell lines, to determine whether the protection is specific for cells derived from different myogenic and non-myogenic sources. Ischemia was simulated by centrifugation of cells into a pellet, and cell viability was determined by hypotonic trypan blue solution. Preconditioning was produced by brief exposures to either glucose-free solution or metabolic inhibition. Freshly isolated rabbit ventricular myocytes were studied to confirm that preconditioning occurs in this model. We then compared these results to those in several cultured cell lines, including HEK 293 cells derived from human embryonic kidney, HIT-T15 cells from Syrian hamster pancreatic islets, and C2C12 cells from mouse skeletal muscle. In the latter cell line, we also determined whether differentiation alters preconditioning. Preconditioning protected rabbit ventricular myocytes: the percentage of dead cells was decreased from 36.8 +/- 4.7% in the control group to 23.0 +/- 5.2% in the preconditioned group after 60 min and from 50.7 +/- 2.1% in the control group to 25.5 +/- 4.5% in the preconditioned group after 120 min ischemia (p < 0.02). In contrast, there was no protection from preconditioning in HEK 293 cells or HIT-T15 cells. Preconditioning did not protect C2C12 myoblasts either. Interestingly, after C2C12 myoblasts had differentiated into myotubes (induced by exposing the cells to low-serum medium), they could then be protected by preconditioning (46.3 +/- 3.6% in the control group vs 26.0 +/- 2.7% in the preconditioned group after 60 min and 67.4 +/- 3.6% in the control group vs 46.0 +/- 4.6% in the preconditioned group after 120 min ischemia; p < 0.05). In conclusion, protection from preconditioning is cell-type specific. The presence of endogenous KATP channels (which are plentiful in HIT-T15 cells) is insufficient to enable preconditioning of the cell. Among the various cell types studied, only differentiated muscle cells (rabbit ventricular myocytes and C2C12 myotubes) exhibited preconditioning.

Animals↗
PubMedDate not supplied

Targeted overexpression of the sarcoplasmic reticulum Ca2+-ATPase increases cardiac contractility in transgenic mouse hearts.

Cardiac hypertrophy and heart failure are known to be associated with a reduction in Ca2+-ATPase pump levels of the sarcoplasmic reticulum (SR). To determine whether, and to what extent, alterations in Ca2+ pump numbers can affect contraction and relaxation parameters of the heart, we have overexpressed the cardiac SR Ca2+-ATPase specifically in the mouse heart using the alpha-myosin heavy chain promoter. Analysis of 2 independent transgenic lines demonstrated that sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA2a) mRNA levels were increased 3.88+/-0. 4-fold and 7.90+/-0.2-fold over those of the control mice. SERCA2a protein levels were increased by 1.31+/-0.05-fold and 1.54+/-0. 05-fold in these lines despite high levels of mRNA, suggesting that complex regulatory mechanisms may determine the SERCA2a pump levels. The maximum velocity of Ca2+ uptake (Vmax) was increased by 37%, demonstrating that increased pump levels result in increased SR Ca2+ uptake function. However, the apparent affinity of the SR Ca2+-ATPase for Ca2+ remains unchanged in transgenic hearts. To evaluate the effects of overexpression of the SR Ca2+ pump on cardiac contractility, we used the isolated perfused work-performing heart model. The transgenic hearts showed significantly higher myocardial contractile function, as indicated by increased maximal rates of pressure development for contraction (+dP/dt) and relaxation (-dP/dt), together with shortening of the normalized time to peak pressure and time to half relaxation. Measurements of intracellular free calcium concentration and contractile force in trabeculae revealed a doubling of Ca2+ transient amplitude, with a concomitant boost in contractility. The present study demonstrates that increases in SERCA2a pump levels can directly enhance contractile function of the heart by increasing SR Ca2+ transport.

Animals↗
PubMedDate not supplied

Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature.

A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

A thematic approach to the history of physiology.

This paper is a brief report of an undergraduate course in the history of physiology. A specific area, the development of the concepts of the cardiovascular system, was examined chronologically through primary readings and laboratory exercises. As an unusual approach to a frequently ignored but important subject, it may be of interest to those concerned with teaching the history of science.

Blood Circulation↗
PubMedDate not supplied

Ion channels: structure and function.

Ion channels are ubiquitous membrane proteins in mammalian cells. Their critical physiological roles include control of the electrical potential across the membrane, facilitation of neuromuscular and neuronal transmission, signal transduction, and regulation of secretion and contractility. The alliance of techniques in biochemistry, electrophysiology, pharmacology, and molecular biology has provided insights into the three-dimensional structure of channel proteins and has allowed specific aspects of functional correlates to be better understood. Promises for the future include molecular genetic approaches to the treatment of disorders such as long QT syndrome and more rational design of drugs targeted to ion channels, including antiarrhythmic agents.

Action Potentials↗