Biomedical subjects

G Trube

Publications and source records attributed to G Trube.

43 records · Page 3Linked to original sources

PubMed1982

Does the organic calcium channel blocker D600 act from inside or outside on the cardiac cell membrane?

The effects of extra- and intracellularly applied D600 (methoxyverapamil) and D890 (a quarternary derivative) on the action potentials of isolated guinea pig myocytes were compared. We also studied the extracellular myocytes were compared. We also studied the extracellular effects of these drugs on the calcium current (hybride sucrose gap) and contractile force of right ventricular trabeculae of the cat heart. The following results were obtained: 1. In ventricular trabeculae D600 suppressed the calcium current, tension and the plateau of the action potential. In contrast, D890 even in a 50 times higher concentration did not display any effect on these parameters. 2. In single isolated cells external application of D890 did not alter the configuration of the action potential. In contrast, external application of D600 suppressed the plateau and shortened the action potential in a dose-dependent way. 3. Intracellular injection of D600 or D890 strongly lowered the height of the plateau and abbreviated the action potential. The onset of the effects of both drugs was more rapid on intracellular application than that of external D600. Whereas the effect of an intracellular injection of D600 was reversible, that of D890 was not. These results support the hypothesis that the organic calcium channel blocker D600 enters the cell in the uncharged lipid soluble form and reaches its receptor associated with the calcium channel from inside. Because of its inability to pass the hydrophobic cell membrane, D890 is ineffective from outside but displays blocking effects on intracellular application.

Action Potentials↗

PubMed1982

Calcium in excitation--contraction coupling of frog skeletal muscle.

A principal step in the process leading to muscle contraction is the intracellular release of Ca2+. We have detected and compared some physical and chemical events that reflect Ca2+ release in contracting frog skeletal muscle cells, described the effects of some agents that are believed to alter intracellular Ca2+ release during contraction, and speculated about the role of Ca2+ release in influencing some of the mechanical properties of frog muscle. The specific physical features recorded were changes in striation spacing, myofibrillar orientation, and force development. The chemical feature was the relative change in intracellular [Ca2+] recorded as light emission from cells microinjected with the Ca2+-sensitive protein aequorin. The presence or absence of a correlation among these variables has been used (i) to evaluate the action of some agents thought to change intracellular Ca2+ release in excitation--contraction (E--C) coupling, (ii) to further substantiate the effects of cell length on Ca2+ release, and (iii) to examine some details of models for E--C coupling. The results showed that potentiating agents enhance and prolong intracellular Ca2+ release without changing the rate of Ca2+ removal during E--C coupling. This extra Ca2+ does not produce the same effect on contractions at all lengths. Contractility is inversely related to cell length, and Ca2+-induced activation is normally less than maximum not only at short lengths but also at optimal striation spacings.

Aequorin↗

PubMed1981

Calcium transients in asymmetrically activated skeletal muscle fibers.

Skeletal muscle fibers of the frog Rana temporaria were held just taut and stimulated transversely by unidirectional electrical fields. We observed the reversible effects of stimulus duration (0.1-100 ms) and strength on action potentials, intracellular Ca2+ transients (monitored by aequorin), and contractile force during fixed-end contractions. Long duration stimuli (e.g., 10 ms) induced a maintained depolarization on the cathodal side of a cell and a maintained hyperpolarization on its anodal side. The hyperpolarization of the side facing the anode prevented the action potential from reaching mechanical threshold during strong stimuli. Variation of the duration or strength of a stimulus changed the luminescent response from a fiber injected with aequorin. Thus, the intracellular Ca2+ released during excitation-contraction coupling could be changed by the stimulus parameters. Prolongation of a stimulus at field strengths above 1.1 x rheobase decreased the amplitude of aequorin signals and the force of contractions. The decreases in aequorin and force signals from a given fiber paralleled one another and depended on the stimulus strength, but not on the stimulus polarity. These changes were completely reversible for stimulus strengths up to at least 4.2 x rheobase. The graded decreases in membrane depolarization, aequorin signals, and contractile force were correlated with the previously described folding of myofibrils in fibers allowed to shorten in response to the application of a long duration stimulus. The changes in aequorin signals and force suggest an absence of myofilament activation by Ca2+ in the section of the fiber closest to the anode. The results imply that injected aequorin distributes circumferentially in frog muscle with a coefficient of at least 10(-7) cm2/s, which is not remarkably different from the previously measured coefficient of 5 x 10(-8) cm2/s for its diffusion lengthwise.

Action Potentials↗

PubMed1981

Experiments with AR-L 115 BS on skinned cardiac fibers.

Cardiac muscle fragments with disrupted sarcolemmas were obtained by homogenizing the ventricles of guinea pig hearts. Force and frequency of the spontaneous contractions of these fragments were measured under control conditions and after adding 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS), caffeine or dihydro-ouabain. The effects of AR-L 115 BS and caffeine were very similar. Probably AR-L 115 BS, like caffeine, releases calcium from the sarcoplasmic reticulum and inhibits the reuptake of calcium.

Animals↗

PubMed1979

Anion dependence of the contractions of skinned cardiac cells.

Cardiac muscle fragments with disrupted sarcolemmas were prepared by homogenization of mouse ventricles. The rate of spontaneous contractions was increased when a solution containing isobutyrate as the main anion was substituted with a solution rich in chloride. At low calcium concentrations preparations which were quiescent in the isobutyrate solution responded to the chloride with a strong single contraction.

Animals↗

PubMed1978

Contractions of skinned cardiac cells elicited by current pulses.

Cardiac muscle fragments with disrupted sarcolemma were prepared by homogenization of mouse ventricles. The preparations exhibited spontaneous contractions of a rate between 3 min-1 and 12 min-1 at 20 degrees C, when they were kept in an appropriate solution. 2. Fragments of about cellular size were attached to two stiff glass microelectrodes, and additional contractions between the spontaneous beats were elicited by current pulses. The duration and intensity of the stimuli were varied to obtain strength-duration curves. Rheobase was in the range of 1.5 muA to 10 muA (no isolation of surrounding bath), chronaxia at 35 degrees C between 30 ms and 80 ms. 3. One microelectrode could be glued to a photodiode-force-transducer for simultaneous recording of contractions and electrical stimulation or potential measurement. Duration of phasic contractions was nearly 1s, force was up to 4muN (20 mN/mm2 of tension).

Animals↗

PubMed1976

Negative inotropic effect of cyclic GMP in cardiac fiber fragments.

The force of spontaneously beating cardiac cellular fragments obtained from mice heart by homogenization was recorded in presence of cyclic guanosine -3'.5'-monophosphate (cGMP) and cyclic 8-bromguanosine -3'.5'-monophosphate in concentrations of 3 X 10(-6) M - 33 X 10(-6) M. The nucleotide decreased the force and reduced the rate of spontaneity. Eventually the preparation became quiescent. It is thought that this nucleotide either reduces the capacity to sequester calcium or affects its release from the sarcotubular system.

Animals↗