100 years of muscle research at Heidelberg. The Kühne-Erb-Hoffmann Symposium, Heidelberg, 25-27 March, 1986.
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Germany↗
Biomedical subjects
R Rüdel
Publications and source records attributed to R Rüdel.
The dynamic sodium current of human skeletal muscle.
The dynamic sodium current (INa) was investigated in intact external intercostal muscle bundles dissected from 5 volunteers. Only fibres with a resting membrane potential negative to -80 mV were used. Stepwise changes were imposed on the membrane potential using the "loose-patch" clamp technique. The following results concerning INa are means +/- SD obtained from 27 fibres: threshold at -42.7 +/- 5.2 mV; maximal amplitude of 9.7 +/- 7.8 mA/cm2 at -1 +/- 13 mV. Inactivation: starting from the resting potential, maximally 90% of INa max could be activated; 50% of INa max were inactivated at Eh = -66.2 +/- 5.8 mV; the slope of the inactivation (h infinity -) curve at this potential was kh = 7.1 +/- 1.6 mV.
Action Potentials↗
The lipid composition of erythrocyte ghosts from a patient with congenital paramyotonia.
The membrane lipid and fatty acid compositions of red blood cells from a paramyotonia patient were investigated. Cholesterol and total phospholipid contents in paramyotonia were not different from control. Only the sphingomyelin content was lower, and thus the molar ratio of phosphatidylcholine/sphingomyelin was higher than normal. The major abnormality concerned the fatty acid pattern. In all the phospholipid classes saturated fatty acids were increased and unsaturated fatty acids were decreased. The overall ratio of saturated/unsaturated fatty acids was 2.1 vs 1.6 in controls. Similar findings have been reported for the sarcolemma from paramyotonia patients. Thus, the results indicate that the membrane defect in this disease may be generalized.
Erythrocyte Membrane↗
In vivo P-NMR spectroscopy: muscle energy exchange in paramyotonia patients.
Using phosphorus nuclear magnetic resonance spectroscopy, we studied the muscle metabolism in four patients with paramyotonia congenita as reflected in the PC/Pi and PC/ATP ratios. At normal body temperature, all results were indistinguishable from controls. After cooling to 29 degrees C muscle temperature and a single 2-sec maximum contraction, the forearm muscles were stiff. At this stage, no decrease in the ATP content could be detected. In greater than 50% of the experiments with patients, an additional peak occurred transiently at the resonant frequency for monophosphates. After a working period at 29 degrees C muscle temperature, the paramyotonic muscles were paralyzed, but displayed spectra similar to those obtained at normal body temperature and full working capability. Intracellular pH was close to 7 in paramyotonic muscle under all conditions examined.
Adenosine Triphosphate↗
Nomograms of the Goldman equation.
Solutions of the Goldman equations for sodium and potassium ions are displayed in nomograms which allow one to determine which values of the variables in the equation (including the activity of the Na/K pump) are compatible with possible steady states of a cell. The nomograms are particularly suited for the study of relative changes of the cell parameters when one or more of them are altered and the cell undergoes a transition from one steady state to another. Special diagrams are presented for finding the changes of the slope conductance (determined at a clamp potential of -80 mV) associated with such transitions. Separate diagrams are given for the cationic component conductance, (gNa + gK), and the anionic component conductance, gCl. The application of the nomograms is illustrated by the exemplary solution of a problem taken from muscle physiology. Further applications of the nomograms are indicated and the limitations of the method are described. The effects of differing activity coefficients in the intra- and extracellular spaces, as well as the contribution of the electrogenic Na/K pump current to the resting potential are discussed.
Cell Physiological Phenomena↗
Membrane changes in cells from myotonia patients.
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Action Potentials↗
Differential effects of succinylcholine and acetylcholine on endplate and extrajunctional membranes of normal and denervated mouse skeletal muscle fibres.
Depolarization provoked by 10(-7)-10(-4) succinylcholine (SCh) and acetylcholine (ACh) was measured in thin bundles dissected from normal and 1-15 days denervated mouse muscles using the microelectrode technique. The muscles were superfused by Cl- -free solutions containing 30 mM K+ to prevent contracture responses. In endplate areas of normal muscles, sensitivity to SCh was roughly 10 times higher than the sensitivity to ACh. By contrast, the extrajunctional membrane of chronically denervated muscles was less sensitive to SCh than to ACh by about the same factor. The extrajunctional membrane of non-denervated soleus muscles was also more sensitive to ACh than to SCh but, unlike the response of the denervated membrane, the depolarization was transient.
Acetylcholine↗
The resting membrane parameters of human intercostal muscle at low, normal, and high extracellular potassium.
Membrane parameters at the respective resting potentials in low, normal, and high extracellular potassium solutions were determined in intercostal muscle fibers from 15 patients with no known neuromuscular disease. In synthetic interstitial fluid (normal potassium concentration 3.5 mmol/liter), we found the following mean values: resting membrane potential RP = -83.3 mV, space constant lambda = 2364 micron, fiber diameter d = 49.3 micron, fiber input resistance Rin = 795 k omega, specific membrane capacitance Cm = 4.7 muF/cm2, and specific membrane resistance Rm = 5970 omega X cm2. The specific membrane conductance was gm = 168 muS/cm2, 76% of it being chloride conductance, 24% being potassium conductance. The dependence of the membrane parameters on the extracellular potassium concentration followed the predictions by the constant field theory. There was no indication of active chloride transport. The resting membrane conductance decreased with temperature with a Q10 of 1.3. Excitability parameters were nearly independent of temperature between 37 and 27 degrees C.
Action Potentials↗
Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters.
To study the mechanism of attacks in familial hypokalemic paralysis, we recorded resting membrane potentials, action potentials, current-voltage relationships, and isometric forces in intercostal muscle fibers from three patients. In normal extracellular medium, the resting potential was reduced, but membrane conductance was not different from control. Excitability was reduced and the action potentials had no overshoot. On exposure to a 1-mM potassium solution, with or without insulin, the cells depolarized to about -50 mV, and became inexcitable. Over the tested membrane potential range from -120 to -40 mV, the slope conductance in the 1-mM potassium solution was not different from that of control fibers in a 1-mM potassium solution. In particular, the potassium component conductance was not reduced. Depolarized fibers could not be completely repolarized by returning to a 3.5-mM potassium solution. An experimentally induced transient shift of the chloride equilibrium potential to a highly negative value caused stable repolarization. Paralysis could also be induced by replacement of extracellular chloride with an impermanent anion, a treatment which causes myotonia in healthy fibers. It was concluded that the basic defects are a reduced excitability and an increased sodium conductance, and that these defects are aggravated on reduction of the extracellular potassium concentration.
Adult↗
Mammalian skeletal muscle: long-lasting contractures and potentiated tetani produced by conditioning with weak acid anions.
Reversible contractures can be induced in slow mammalian muscles by manipulations that probably generate a long-lasting alkalinization of the muscle cell interior. Such contractures reach about 1/4 of the tetanic force, P0, and last 10 times longer than potassium contractures. While in contracture, the muscle fibers have high resting potentials so that they can be electrically stimulated. Tetanic force is then increased and added to that of the contracture so that total force may reach 2 P0. This level of potentiation has not been reached by any previously-known method.
Animals↗
Two cases of adynamia episodica hereditaria: in vitro investigation of muscle cell membrane and contraction parameters.
Membrane potentials, current-voltage relationships, and contractile parameters were studied in intact muscle cell bundles obtained from two patients with adynamia episodica hereditaria. In a normal extracellular medium, the cell membranes had resting potentials of about -80 mV and their current-voltage relationships were not significantly different from control curves. In contrast to normal muscles the afflicted cells were paralyzed in a medium having 6-10 mmol/liter potassium. The mechanisms of paralysis in the two specimens were different from each other. Many fibers from one patient were spontaneously active even in normal solution. In high potassium solution spontaneous activity was increased and the cells gradually depolarized to values at which excitatory sodium current is normally inactivated. This depolarization was connected with an increased sodium conductance and was reversed by the application of tetrodotoxin (TTX). The fibers from the other patient were not spontaneously active. In high potassium solution they were paralyzed at membrane potential values at which normal fibers would still contract. The reason for this paralysis was a reduced excitability.
Adolescent↗
Influence of divalent cations on potassium contracture duration in frog muscle fibres.
Single fibres or small fibre bundles were dissected from twitch muscles of frogs and washed in low Cl-solutions. Contractures were provoked by 122.5 mM K+. At room temperature (17-20 degrees C) the contracture duration was about 1.5 s in the absence of divalent cations and about 3 s in the presence of 2 mM Ca2+. Contractures were prolonged when Ca2+ was replaced by Ni2+ showing that inward Ca current was not the factor responsible for the contracture prolongation. K contracture duration was prolonged in the cold (3 degrees C) by a factor of about 4 in the presence of non-permeating divalent cations (Ni, Co), when 0.1 mM La3+ was applied together with 2 mM Ca2+, and in the virtual absence of divalent cations. The contractures were prolonged in the cold by a factor of 6 or more in the presence of permeant divalent cations (Ca, Sr, Ba, Mg, and Mn at 8 mM). Diffusion of divalent cations in the transverse tubules of the muscle fibres was shown to have a Q10 similar to that in free solution. It was concluded that inward current of divalent cations may shorten contracture duration by causing ionic depletion of the transverse tubules.
Animals↗
A simple method for controlling the fluid level in a small experimental chamber during slow and rapid fluid exchange.
A simple and cheap method is devised for controlling the fluid level in an open chamber for physiological or other experiments. Fluid is pumped into the chamber at variable flow rate using a conventional pump. Autoregulated drainage is achieved through a capillary tube whose bevelled opening is covered with a net with fine meshes. Part of the opening dips into the fluid surface. The correct amount of fluid is sucked out of the chamber by a constant negative pressure at the back of the tube. The 1 mm depth of a 2 microliters volume stays within +/- 2% when the normal flow of 1 microliters/s is doubled and halved, respectively. A 100-fold increase of flow, as needed for flushing the chamber, causes a rise of the surface level by 0.5 mm only.
Animals↗
Branched skeletal muscle fibers not associated with dysfunction.
We report the occurrence of large clefts and branches in some amphibian vertebrate skeletal muscle fibers. Such fibers can be isolated intact from various skeletal muscles of fully mature animals and apparently are normal in other respects. Electron micrographs showed no signs of degeneration in most fibers. Electrical and mechanical studies revealed that all branches were excitable and able to contract. Branches evidently can arise in the absence of abnormal influences such as experimentally induced overload. The apparent cause may be either fusion or splitting of fibers.
Animals↗
The electrogenic sodium pump in guinea-pig ventricular muscle: inhibition of pump current by cardiac glycosides.
1. The inhibition of the electrogenic sodium pump in guinea-pig ventricular muscle by cardiac glycosides was studied with a voltage-clamp technique.2. Superfusion of the preparation with dihydro-ouabain (DHO) produced a reversible depolarization of up to 7 mV. When the membrane potential was clamped to a constant value near the resting potential application of DHO produced a corresponding current change in the inward direction which reached a steady state in less than 1 min.3. The drug-induced current change (I(D)) was found to be the result of a parallel shift of the current-voltage relation. The contributions of a change in extracellular K or intracellular Na to the measured I(D) were shown to be very small. From these findings and the results summarized below it was concluded that I(D) represents the blockage of the electrogenic pump current by DHO and that it is proportional to the number of drug molecules bound to the Na-K-ATPase in the intact cell.4. The dependence of I(D) on the concentration of DHO applied (5 x 10(-6)-8 x 10(-4) M) was found to be consistent with the predictions of the law of mass action for reversible one-to-one binding of the drug to the Na-K pump under equilibrium conditions. From a Scatchard-type plot the equilibrium dissociation constant (K(D)) of DHO was determined to be 4.6 (+/-2.3) x 10(-5) M.5. The steady-state pump current in the resting preparation was calculated to be 0.81+/-0.26 muA/cm(2). It contributed 6.4+/-0.9 mV to the resting potential in Tyrode solution containing 3 mM-K.6. In the smallest preparations used the measured time course of the onset and decay of I(D) agreed with the chemical kinetics of binding and unbinding calculated for various DHO concentrations. The rate constant of unbinding (k(2)) was found to be 3.4 (+/-0.7) x 10(-2) S(-1) and the average rate constant of binding (k(1)) was 7.4 x 10(2) M(-1) S(-1).7. By comparing the effects of ouabain and DHO in the same preparation the following estimates of the chemical constants of ouabain binding to the Na-K pump were obtained: K(D) approximately 1.5 x 10(-6) M; k(1) approximately 4 x 10(3) M(-1) S(-1); k(2) approximately 6 x 10(-3) S(-1).8. An analysis of the transmembrane movements of Na and K in the steady state showed that the measured pump current density is consistent with a counter-transport of 3 Na and 2 K ions.
Animals↗
Cardiac glycoside binding to the Na/K-ATPase in the intact myocardial cell: electrophysiological measurement of chemical kinetics.
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Animals↗
Effects of AR-L 115 BS on arterial and venous muscle tone in vitro.
The effects of the cardiotonic drug 2-[(2-methoxy-4-methyl-sulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) on strips from isolated human veins and on strips from bovine veins and arteries were studied. The effects depended on the type and on the site of origin of the vessel. Pre-stretched human saphenous vein strips always relaxed in presence of AR-L 115 BS (greater than 10(-4) mol/l) while jugular vein strips seemed rather unaffected. Pre-stretched bovine facial vein strips always relaxed in presence of AR-L 115 BS, proximal branches being significantly more sensitive to the drug than distal branches. In bovine facial arteries AR-L 115 BS (greater than 10(-4) mol/l) produced either no change or a small increase in tension. When the arteries were pre-contracted by application of 50 mmol/l K+, low concentrations (less than 10(-5) mol/l) increased the tension while high concentrations (greater than 10(-5) mol/l) induced relaxation. The relaxing power of AR-L 115 BS on pre-contracted vein strips seemed better than that of nifedipine and less than that of Na nitroprusside.
Acetylcholine↗
Improved therapy of myotonia with the lidocaine derivative tocainide.
The antimyotonic effect of the antiarrhythmic drug tocainide was tested in 14 patients. With 1200 to 1600 mg/d all patients reported good improvement. This was substantiated by objective tests. Only four patients noticed minor side effects.
Adolescent↗