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E E Carmeliet

Publications and source records attributed to E E Carmeliet.

16 recordsLinked to original sources
PubMed1997

Neurospecificity of phyto-bufadienolides is not related to differences in Na+/K+ pump inhibition.

The aim of the present study was to investigate the effects of neuro- (cumulative) and cardiotoxic (non-cumulative) bufadienolides originating from plants (phyto-bufadienolides) on the Na+/K+ pump current (Ip) in cardiac (rat and guinea pig) and dorsal root ganglion cells (guinea pig), and on Ca2+ currents in cardiomyocytes (guinea pig). All bufadienolides tested (non-cumulative drugs: thesiuside, tyledoside C; lanceotoxin B and tyledoside F for the neurotoxic group) were potent blockers of Ip at concentrations in the micro- and submicromolar range. K0.5 values for Ip inhibition in dorsal root ganglion neurones were slightly lower compared to cardiomyocytes, but the order of potency was similar in both cell types. Both classes of bufadienolides were equipotent in suppressing Ip, generated by high- and low-affinity pump isoforms. Phenomena related to pump inhibition, as hypercontracture and increase in T-type Ca2+ current in cardiomyocytes, were influenced to the same extent. Therefore, from these results, neurospecificity of some bufadienolides could not be explained by differences in Na+/K+ pump affinity.

Animals↗
PubMed1990

Reduction of ischemic K+ loss and arrhythmias in rat hearts. Effect of glibenclamide, a sulfonylurea.

Glibenclamide, one of the antidiabetic sulfonylureas, is known to block ATP-dependent K+ channels. We used this drug to determine to what extent K+ loss from acutely ischemic myocardium is mediated via these channels. We also investigated whether glibenclamide would influence ischemic arrhythmias. Isolated rat hearts rendered globally ischemic showed no correlation between early lactate and K+ efflux rates. Cumulative K+ loss during 11 minutes of global ischemia (0.5 ml min-1 g-1) was reduced, from 3.2 +/- 0.3 to 2.5 +/- 0.1 mueq/g (p less than 0.025) by 1 microM glibenclamide and from 3.3 +/- 0.2 to 1.9 +/- 0.2 mueq/g (p less than 0.005) by 10 microM glibenclamide, while lactate efflux was unaltered by the drug. Glibenclamide also exhibited potent antifibrillatory activity, abolishing irreversible ventricular fibrillation during regional ischemia (0/6 vs. 5/6 controls; p less than 0.02) and during global ischemia (0/7 vs. 9/9 controls; p less than 0.01). Heart rate, coronary flow rate, peak systolic pressure, and myocardial oxygen consumption were unaltered by the drug (1 microM). Similarly, glibenclamide (1 microM) did not alter myocardial ATP, phosphocreatine or lactate content, or glucose utilization. Ventricular fibrillation threshold during normoxia was also unaltered by glibenclamide (1 microM). We conclude that K+ loss during acute myocardial ischemia is mediated partly by ATP-dependent K+ channels, and not by a tightly coupled co-efflux with anionic lactate.

Animals↗
PubMed1979

Epinephrine and the pacemaking mechanism at plateau potentials in sheep cardiac Purkinje fibers.

1. In 1.35 mM [K+]0, sheep cardiac Purkinje fibers depolarized to about -40 mV. Whereas some fibers oscillated spontaneously at plateau potentials, others could be made to oscillate when polarized by intracellular currents. Pacemaker activity at plateau potentials (-50 to 0 mV) was distinct from that caused by the iK2 pacemaker at more negative potentials (-60 to -100 mV). 2. Epinephrine induced spontaneously occurring action potentials and increased pacemaker activity in depolarized Purkinje fibers. The ED50 for the positive chronotropic effect of epinephrine was about 5 x 10(-7) M. This concentration is similar to that reported for the effect of epinephrine on plateau amplitude (Carmeliet and Vereecke, 1969) and the slow inward current (isi, Reuter, 1974). 3. In voltage clamp experiments, epinephrine, increased the magnitude of isi and of an outward plateau current, ixi. It is concluded that epinephrine effects pacemaking at plateau potentials by increasing isi and without shifting the voltage dependence of these currents. The onset of pacemaker activity by epinephrine was preceded by membrane depolarization that results from an inward shift of the steady-state current-voltage relation. This current may flow through isi channels that are activated but not completely inactivated.

Animals↗
PubMed1976

Developmental aspects of potassium flux and permeability of the embryonic chick heart.

1. The rate coefficient of 42K efflux, the transmembrane potential, the intracellular concentrations of Na and K and the volume/surface area have been measured in embryonic chick hearts of different ages. 2. With respect to age, the rate coefficient for 42K efflux was minimal for preparations from 6-8 day old embryos, and distinctly higher values were obtained for the hearts of 3-5 and 18-20 days. With respect to the effect of external K concentration (Ko), all age groups showed a five- to sevenfold increase in rate coefficient between 2-5 and 140 mM-Ko. The effect of Ko was found to be indepedent of extracellular Na, except in the 18-20 day hearts bathed in K-free solution. 3. Intracellular concentrations of K and Na were found to decrease, membrane potential to increase with age. The volume/surface area measured by stereologic and morphometric techniques did not change with age. 4. The permeability coefficient for K (PK), calculated from the absolute K flux and the measured membrane potentials, was fairly constant for a given age between 2-5 and 20 mM-Ko. In K-free solution, PK was markedly reduced (factor 4). At a given Ko, PK increased twofold between 6-8 and 18-20 days while PNa remained relatively constant.

Animals↗
PubMed1975

Increase of potassium flux by valinomycin in embryonic chick heart.

The effect of different concentrations of the antibiotic valinomycin, was determined on 42K efflux and Na, K content of embryonic chick hearts. Valinomycin produces an increase of K efflux which is progressive in time and markedly dependent on the concentration of external K (0-5 mM) and valinomycin (10(-8) to 10(-5) M). The changes in K efflux is not due to a reversal of the Na-K pump mechanism, secondary to ATP depletion: i) the increase of K efflux by valinomycin persists in the absence of external Na ions. ii) analysis of Na and K content and 42K influx measurements with and without valinomycin indicate that active K influx is not inhibited in a solution containing 0.5 mM K and only slightly decreased in a solution containing 5 mM K. Valinomycin, acting as a K carrier, presumably increases K conductance of the cell membrane resulting in a rise in K efflux.

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