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Biomedical subjects

W Trautwein

Publications and source records attributed to W Trautwein.

At least 91 records · Page 5Linked to original sources
PubMed1980

On the mechanism of slow calcium channel block in heart.

1. D600 (methoxyverapamil, 2 x 10(-6) M) has little activity when it is applied during a rest interval. Its ability to depress Isi and contraction is much reduced when the muscle is rested. 2. Upon each activation the blockade of the slow channel increases until the use-dependent increase of blockade equals the diastolic removal, thus resulting in a frequency-dependent steady-state blockade. 3. Removal of block during a variable rest interval at various holding potentials is the faster the more negative the holding potential and gets slower in the more positive and gets slower in the more positive potential range. This process can be described by two voltage-dependent time constants (tau 1, tau 2). Similarities in the action of D600 on the si-channel to the action of local anaesthetics on the Na+-channel in nerve and heart are pointed out.

Animals↗
PubMed1978

Relaxation of the ACh-induced potassium current in the rabbit sinoatrial node cell.

Voltage clamp experiments were carried out in order to study the mechanism of the ACh action in the rabbit S-A node cell. The following results were obtained: 1. The reversal potential of the ACh-induced current behaved like a potassium electrode, confirming that the ACh-operated channels pass potassium ions selectively. 2. On depolarizing voltage jumps the ACh-induced current showed an instantaneous peak from which the current decayed to a new steady level (relaxation). On hyperpolarizing voltage jumps the initial step change in current was followed by a gradual increase. 3. The time course of the current change on voltage jumps was well fitted by a single exponential and the time constant became longer as the membrane potential was increased. 4. The instantaneous I-V curve was linear while in the steady state the curve became flatter at low negative membrane potentials and steeper at high negative membrane potentials. The results suggest that ACh opens a specific potassium channel when the drug is bound to the muscarinic receptor. The opening and closing rate constants for this potassium channel depend on the membrane potential in such a way that on depolarizing voltage jumps the fraction of open channels gradually decreases and on hyperpolarization the fraction increases.

Acetylcholine↗
PubMed1978

Current-voltage relations in ventricular muscle preparations from different species.

Current-voltage relations were determined in ventricular muscle preparations from dog, sheep, pig, guinea pig, bull and cat hearts. The single sucrose gap voltage clamp method was used to apply 2 s steps or slow speed voltage ramps (3-4 mV/s). 1. The current-voltage relations obtained with 2 s steps were similar to those obtained with ramps. 2. Negative slope regions were readily apparent in the current-voltage relations of preparations from all species except cat although the latter did display marked anomalous rectification. 3. Increasing the external potassium concentration from 3 to 10 mM increased the slope of the current-voltage relation around the resting potential and resulted in the "crossing-over" and "crossing-back" of the relations if all tissues. 4. The two extreme cases of bull (marked negative slope region) and cat (no negative slope region) were compared with regard to transgap intracellular and extracellular resistances; they were quite similar. This suggests that the current-voltage relations reflect differences in membrane properties rather than, for example, different proportions of non-membrane leakage current. 5. In bull ventricular preparations, the application of D-600 (2 X 10(-6) M), 30 min) had only a small effect on the current-voltage relation. In contrast, cesium (10-20 mM) nearly abolished the negative slope region suggesting that this characteristic of the current-voltage relation is due to potassium channel rectification. 6. Possible explanations for action potential durations in bull ventricular fibres being 50 to 100% longer than in cat are considered.

Action Potentials↗
PubMed1978

Membrane currents in cat myocardium: separation of inward and outward components.

1. The single sucrose gap method was used to control the membrane potential of cat ventricular fibres.2. Following the early rapid events (capacitive, Na and slow inward (si) current spikes) the membrane current on depolarization contained three time-dependent components which appeared attributable to the inactivation of I(si) and the activation of two outward currents labelled I(K) and I(x).3. Tail currents were analysed with a view to confirming these conductance changes. At -60 mV the tail progressed from being predominantly inward in direction after short (30-50 msec) depolarizations to being predominantly outward after long (> 300 msec) depolarizations. Inward and outward components decayed exponentially with time constants independent of previous membrane history. The Q(10)s were about 3.4. Experiments with D600 and variations of the driving force identified the inward tail component (tau approximately 55 msec at -60 mV) as I(si). The major outward tail component (tau approximately 300 msec) appears to be carried primarily by potassium. A second outward tail component (tau approximately 3 sec) of much smaller amplitude than I(K) was observed after long depolarizations and is tentatively labelled I(x).5. Membrane currents at 0 mV can be described as the sum of three exponential processes: I(si) inactivation (tau approximately 90 msec), I(K) activation (tau approximately 370 msec) and I(x) activation (tau approximately 3 sec). Conductance measurements (envelops of I(si) and I(K) tails) supported these time courses. I(si) time constants increased from 50 msec at -40 mV to 120 msec at +40 mV. I(K) time constants increased from 400 msec at -40 to about 520 msec at -25 mV before declining to 300 msec at +40 mV.6. I(si) amplitudes measured visually (difference between peak I(si) and current level after 200-500 msec) were compared with those measured graphically (semilog plots, subtraction of I(K) and I(x)). As a consequence of the relative amplitudes and time courses of I(si) and I(K), the shapes of the I(si) voltage relations were not markedly different: visual estimates at 200 msec were in agreement with graphic estimates, visual estimates at 300 or 500 msec exceeded these by 15-30% between -20 and +20 mV.

Animals↗
PubMed1978

The potassium current underlying delayed rectification in cat ventricular muscle.

1. Outward currents in cat ventricular fibres have been studied using the single sucrose gap method. The time dependent outward currents can be separated into a fast component, I(K), and a slow component, I(x). The voltage dependence of the I(K) time constant was bell-shaped, being about 150 msec at -90 mV, 500 msec at -25 mV and 300 msec at +30 mV. The combination of much faster time constants and larger amplitudes relative to I(x) allowed the estimation of I(K) amplitude, but not time course, from semilog plots of membrane currents accompanying 2 sec depolarizations.2. The ;steady-state' outward current at 2 sec (I(ss)) was separated into time independent background current (I(bg)) and time dependent I(K). The activation threshold for I(K) was about -50 mV and its amplitude increased steeply between -30 and +10 mV. The ratio of I(bg) to I(K) was about 1 between -30 and +30 mV.3. The current-voltage relations of I(ss) and I(bg) showed inward going rectification but negative slope regions were not observed. Raising the external K concentration from 3 to 10, 20 and 30 mM increased conductance and induced ;cross-overs' in the current-voltage relations. Increases in conductance were offset by the reductions in driving force, i.e. currents at plateau potentials were not larger in high K solutions.4. K accumulation occurs in response to prolonged membrane depolarization but conductance rather than accumulation appears to be responsible for the slowly rising outward current, I(x). However, the accumulation which takes place during the activation of I(x) may preclude an accurate determination of its time course and reversal potential.5. The potential at which outward I(K) tails declined to zero was strongly dependent on external K concentration in the range 3-30 mM. Inward going I(K) tails were difficult to detect because control hyperpolarization from the resting potential triggered large inward time dependent currents. Evidence is presented suggesting that much of this time dependency is due to the depletion of extracellular K from regions of restricted diffusion.6. The steady-state activation variable (n(infinity)) of the I(K)-system had to be calculated from isochronic (300 msec activating pulses) activation relations and tau(n)s because shifts in V(K) due to K accumulation precluded complete activations. The shape of n(infinity) was sigmoid approaching 0 at -60 mV, 0.5 at -20 mV and 1 at +20 mV.7. The fully activated current-voltage relation of I(K) displayed inward going rectification.8. It is concluded that there are strong similarities between I(K) in ventricular muscle and i(x1) in Purkinje fibres. Possible counterparts in frog atrial muscle include the currents labelled I(1) and i(x.slow).

Animals↗
PubMed1977

On the mechanism underlying the action of D-600 on slow inward current and tension in mammalian myocardium.

D-600 the methoxy derivative of verapamil, is said to affect the force of cardiac contraction and the slow inward current (LSi) specifically by reducing the membrane conductance for Ca2+ (gsi). However, it is apparent that many effects of D-600 cannot be adequately explained solely by an effect on gsi. We studied the effects of D-600 on membrane current and tension of cat papillary muscle, using a conventional single sucrose gap voltage clamp technique. The results indicate that D-600 not only reduces the maximal Ca conductance but also, depending on concentration and duration of exposure, alters both the kinetics of the Ca-carrying system and the amplitude of the steady state outward current. No changes in the steady state activation and inactivation variables or in the rate of Isi inactivation were found. However, a substantial increase in the time to peak Lsi, as much as 7 times normal, was observed after exposure to D-600 (0.5 X 10(-6) to 2.0 X 10(-6) M) for at least 20 minutes. Because approximately only 75% of the reduction in Lsi induced by D-600 could be attributed to change in the maximum value of gsi (gsi), we conclude that the change in time to peak and about 25% of the reduction in Isi must be due to a change in the activation kinetics of the Ca-carrying system, Calculations suggest that the time to 70% activation of gsi can be prolonged to as much as 10 times normal by prolonged exposure to negatively inotropic concentrations of D-600.

Action Potentials↗
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↗
PubMed1976

On the mechanism of the negative inotropic effect of acetylcholine.

The negative inotropic action of ACh was investigated by voltage clamping mammalian atrial myocardium with the single sucrose gap method. Acetylcholine (ACh) affected the outward current, slow inward current and clamp tension in a concentration dependent way. 1. Concentrations of ACh which reduced action potential twitch tensions by up to 30 or 40% (ED-30-ED-40) increased steady state outward currents but had no effect on the time dependent outward current, the slow inward current or voltage clamp tension. This indicates that in this dose range the negative inotropy during normal activity can be completely explained by an "indirect" effect on the slow inward current, i.e. increased outward current shortens the action potential and prevents the slow inward current from running its normal time course. 2. Higher concentration of ACh (ED-70-ED-90) greatly increased the steady state outward currents and abolished anomalous rectification without affecting delayed rectification. The slow inward current and voltage clamp tension were reduced indicating that in this concentration range a 'direct' effect of ACh on the slow inward current and tension may be expected to add to the 'indirect' effect mentioned above.

Acetylcholine↗
PubMed1975

Temperature sensitivity of outward current in cardiac Purkinje fibers. Evidence of electrogenicity of active transport.

1. In cardiac Purkinje fibers the temperature sensitivity of the membrane current flowing after 2 sec in response to depolarizing clamp steps was recorded. When the temperature was quickly lowered (30 sec) from 37 degrees C to 20 degrees C for a period of 2 min the outward current was markedly reduced. The effect was immediately reversed upon rewarming. The reduction in outward current on cooling was most pronounced between 30 degrees C and 20 degrees C. 2. In the range of anomalous rectification cooling to 20 degrees C shifted the i.v. relation in a negative direction by a constant amount of 20 nA. Outside this potential range (negative to -80 mV and positive to -45 mV) the slope conductance was reduced with a Q10 of about 1.3. 3. In the presence of dihydroouabain cooling did not further reduce the outward current in the potential range of anomalous rectification. However, negative to -80 mV and positive to -40 mV the slope conductance was reduced. The results support the view that part of the outward current is generated by an electrogenic sodium pump which is inhibited by cooling.

Animals↗
PubMed1975

Calcium conductance and tension in mammalian ventricular muscle.

Voltage, membrane current and contraction were simultaneously measured in voltage clamp experiments (single sucrose gap) on cat ventricular trabeculae. The pulse programs allowed the determination of the potential dependence of the steady state activation and inactivation as well as the restoration of the calcium-carrying system (slow inward current). 1. The steady state activation variable (d infinity) rose in a sigmoid manner from -50 mV (d infinity nearly 0) to 0 mV (d infinity nearly 1). The experimental values can be described by the function 1/1 + exp [(Vh-V)/S] where half activation (Vh) = -22.5mV and S = 7.6 mV. 2. The steady state inactivation variable (f infinity) declined from 1 at -60mV to 0 at 10mV. The best fit curve is nearly a mirror image of the activation curve with Vh = -28 mV and s = -8.3 mV. 3. The voltage dependence of the (normalized) peak tension was well described by the steady state conductance variables except at potentials positive to +20mV. A "steady state" tension (superimposed on "tonic tension") was found in the potential range where a steady state conductance is predicted by the curves describing steady state activation and inactivation. 5. Following inactivation, the time courses of restoration of the calcium-carrying system and tension were identical. Time courses were exponential with tau = 118 msec at -80 mV, 144 msec at -60 mV, and 198 msec at -40 mV. 6. Two possible models of excitation-contraction coupling in line with the present results are discussed.

Animals↗
PubMed1975

Membrane currents and tension in cat ventricular muscle treated with cardiac glycosides.

The effect of cardiac glycosides on membrane currents and tension in cat ventricular muscle was studied using the single sucrose gap voltage clamp method. Complete tension-voltage and current-voltage relations were obtained in five preparations before and during treatment with dihydro-ouabain (DHO, 1.7 X 10(-5)M). After 1-2 minutes of DHO, the developed tension was 15% greater than control, but there was no change in either the slow inward (calcium) current (Ica) or the level of the outward current flowing at the end of a 300-msec depolarization (Iout). After 6-8 minutes of DHO, there was a 60% increase in developed tension, a noticeable increase in resting tension, a 20% decrease in Ica, and a smaller increase in Iout. It seems possible that the reduction of Ica was due to a reduced driving force. In preparations treated with ouabain (5 X 10(-7)M, 3-5 minutes), developed tension was 45-150% greater than control with no change in Ica or Iout between -45 and + 15 mv. We conclude that the inotropic action of these cardiac glycosides is not mediated by an increase in Ica.

Animals↗
PubMed1975

Outward current and electrogenic sodium pump in Purkinje fibers.

The effects of metabolic inhibitors (ouabain, dihydroouabain, and 2,4-dinitrophenol (2,4-DNP) and of cooling on the membrane current of Purkinje fibers were studied by means of a voltage clamp. Within seconds after cooling or application of the drugs the outward current was found to be reduced. On longer cooling or poisoning, the potassium equilibrium potential was shifted in positive direction, the time-dependent membrane currents were depressed, and possibly the potassium conductance was altered. It is suggested that the early reduction in outward current is caused by inhibition of an electrogenic sodium pump.

Action Potentials↗