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Acid-base changes and excitation-contraction coupling in rabbit myocardium. II. Effects on resting membrane potential, action potential characteristics and propagation velocity.

The effects of changes in acid-base parameters on the resting membrane potential, action potential characteristics and propagation velocity were studied in isolated rabbit papillary muscles. Lowering extracellular pH from 7.4 to 6.7 in a bathing solution buffered with 10 mM histidine did not alter the resting membrane potential or action potential characteristics but casused slight reduction in propagation velocity. A parallel increase in HCO3-minus concentration (up to 47 mM)and PCO2 at a constant extracellular pH of 7.4 caused a substantial decrease in action potential duration but did not alter the resting membrane potential or propagation velocity. The decrease in action potential duration was caused by the increase in HCO3-minus concentration. Propionate (47nM) caused a shortening of the action potential which was of the same magnitude as for HCO3-minus but methylsulfate (47nM) did not have this effect. The possible influence of these changes on the inotropic state of the myocardium and the cellular mechanisms involved are discussed.

Action Potentials

Frequency and time domain characteristics of single muscle fibre action potentials.

Action potentials of single muscle fibers (brachial biceps) were recorded with a multi-electrode, ensuring a minimum fibre-electrode recording distance. Propagation velocity was measured in 15 fibres and the power spectral density of the action potentials was computed through a FFT algorithm. Linear correlation was found between action potential amplitude (peak to peak) and propagation velocity, as well as between maximum-minimum amplitude time (defined as the time interval between the positive and negative peaks) and propagation velocity. Assuming al linear dependence between propagation velocity and muscle fibre diameter, a linear relation between the fibre thickness and the extra-cellular action potential was derived from the action potential amplitude/propagation velocity curve. The action potential power spectrum had a band pass form, with peak magnitude of 1.61+/-0.03 kc/sec, and -3 dB points at 0.98+/-0.19 kc/sec and at 2.41+/-0.53 kc/sec. A linear relation was found between the spectral peak magnitude and propagation velocity, and between the ban width and the propagation velocity, as predicted by a mathematical model describing the power spectrum of single fibre action potentials.

Action Potentials

[Resting potential and action potential of an individual frog muscle fiber during reciprocal inhibition].

In single muscle fibres of the frog m. tibialis anticus longus resting membrane potential and parameters of the action potential were studied in situ during rest and during the resiprocal inhibition of its spinal center. Development of the reciprocal inhibition increased the resting membrane potential, the amplitude of the action potential, but decreased the time course and latency of the action potential. The changes in functional properties of single muscle fibres seem to occur as the result of deprovation of central influences due to the reciprocal inhibition.

Action Potentials

[Changes in transmembrane action potentials and monophasic action potentials of phase 3 intraventricular block in rabbits].

The model of phase 3 intraventricular block was produced in 10 rabbits by giving 2.5% solution of potassium chloride intravenously under natural breathing and sinus rhythm. Transmembrane action potentials and monophasic action potentials were recorded respectively. The results showed that RP, APA, Vmax, MAPA and MVmax all decreased and both APD and MAPD shortened at the time of ventricular conduction block, when ventricular conduction was improved by vagal stimulation, RP, APA, Vmax, MAPA and MVmax all increased and both APD and MAPD lengthened. In addition, APD and MAPD measured at the same site in normal conduction, conduction block and conduction improved by vagal stimulation were in consensus.

Action Potentials

Lidocaine effects on action potentials of Purkinje fibers from neonatal and adult dogs.

We studied the effects of lidocaine (L), 2 to 40 mg/l, on the cellular electrophysiologic properties of Purkinje fibers (PF) from neonatal (0-10 days) and adult dogs. Microelectrode impalements of neonatal and adult PF were selected so that there were no differences between the two groups in control maximum diastolic potential, action potential amplitude and maximum upstroke velocity of phase 0 depolarization (Vmax). However, control action potential duration was significantly shorter in neonates than in adults (P less than .05). At a superfusate [K+] = 4 mmol/1, the threshold concentration for L effects on action potential amplitude in neonates was 40 mg/1 and in adults, 20 mg/1; on Vmax in neonates threshold was 5 mg/1 and in adults was 2 mg/1; on action potential duration in neonates and adults threshold was 2 mg/1. For all variables studied the effect of L on adult PF action potentials was greater than on neonatal PF. The effects of L on action potential duration also suggest that potassium conductance may be greater in neonatal fibers. When superfusate [K+] was increased to 6 mM the effects of L on adult PF were potentiated more than on neonates. These results provide further experimental evidence of the age-related changes in sensitivity of the specialized conducting system to cardioactive drugs.

Action Potentials

Development of endocochlear potential and compound action potential in the rat.

The present study was designed to investigate the developmental changes of the endocochlear potential and compound action potential simultaneously from rat pups of various ages. Animals were anesthetized with ketamine/xylazine, and the endocochlear potential was measured with a glass microelectrode. At the same time, a wire electrode was placed on the round window to record the click-evoked compound action potential. The endocochlear potential was found to be very low during the first few days of postnatal life. A rapid increase in the value of the endocochlear potential was noted between eleven and thirteen days of age, and adult-like values were recorded by seventeen days of age. Compound action potential responses were recorded at thirteen days of age to high intensity clicks, followed by a progressive improvement of thresholds and reduction of latencies. The development of the endocochlear potential and compound action potential was found to be reciprocally related - as the magnitude of the endocochlear potential increased, the compound action potential threshold declined with increasing age. The development of the endocochlear potential was found to closely approximate the development of enzymatic activity of sodium, potassium-ATPase in the stria vascularis reported by Kuijpers (1974).

Action Potentials

[Effects of furosemide on endocochlear potentials, auditory action potentials and summating potentials and the changes of inner ear pathology].

Guinea pigs were injected with furosemide 50 mg/kg (group A) and 25mg/kg (group B). Two minutes after injection, EP of group A decreased to -13.9mv while that of group B decreased to +65 mv. Also, AP of group A disappeared, and recovered at 8.5 mins. while AP amplitude of group B decreased to 78%. The SP value of group A changed from -14.5mv to +23.4mv 1 min after injection and returned to negative polarity in 12 min. Edema of stria vascularis was observed under light microscope. Transmission electron microscope showed edema between marginal cells and intermedia cells, cytoplasm of the marginal cell protruded to the cochlear duct, and cell membrane of outer hair cell folded. The finding of this study illustrates that furosemide inhibits the transportation of the active ions of cochlear duct tissue resulting in decrease of EP and alters the function of hair cells causing the change of AP amplitude. -SP depends on the ion transportation, the polarity can be inversed while large dosage of furosemide was used.

Action Potentials

Reperfusion arrhythmias in isolated perfused pig hearts. Inhomogeneities in extracellular potassium, ST and TQ potentials, and transmembrane action potentials.

We recorded direct current electrograms and local [K+]o at multiple sites and transmembrane potentials at selected sites during reperfusion after 5 minutes and 10 minutes of regional ischemia in isolated perfused pig hearts. After 10 minutes of ischemia, the incidence of ventricular fibrillation (VF) was 38%. At 80-90 seconds after reperfusion, [K+]o was 0.8 mM less than in normal tissue in half of the reperfused tissue, especially in the border zone. This was associated with TQ elevation of +4.5 mV and large peaked T waves. The latter was caused by an abrupt decrease of action potential duration in reperfused tissue, leading to a difference of up to 165 msec with normal tissue. Reperfusion VF started with a closely coupled ventricular premature beat. Activation block between reperfused and normal tissue permitted reentrant activation, leading to VF. Pretreatment with ryanodine (10(-6) M) and reperfusion with elevated [K+] (both of which prevent delayed afterdepolarizations) did not prevent closely coupled ventricular premature beats or VF. Five minutes of ischemia never caused VF. K+ depletion and TQ elevation in the reperfused zone was less frequent and smaller (-0.4 mM and 1.8 mV, respectively). Peaked T waves did not occur, and shortening of the action potential duration was less. We conclude that extracellular K+ depletion and marked action potential duration shortening in the reperfused tissue play a role in the genesis of reperfusion VF, which is caused by reentry. The closely coupled ventricular premature beat that initiates reentry is not caused by delayed afterdepolarizations but most likely by intramural reentry.

Action Potentials

Ionic currents contributing to the action potential in single ventricular myocytes of the guinea pig studied with action potential clamp.

With the action potential clamp procedure we studied the contribution of various ionic currents to the action potential in single ventricular myocytes. Action potentials were elicited by a current pulse through the suction pipette and recorded by a computer. A representative action potential was then repetitively replayed to the same cell under voltage-clamp conditions. Successive pharmacological blocks of ionic currents allowed for the first time the measurement of the contribution of the L-type calcium current (ICa) and the [Ca2+]i-activated currents as well as the potassium current to the action potential. Experiments using caffeine as a tool to increase calcium release from the sarcoplasmic reticulum supported the idea that INaCa contributes to the plateau during the second half of the action potential and even lasts into diastole, whereas strong elevation of the intracellular [Ca]i during the action potential additionally activated the non-specific cation channel.

Action Potentials

Far-field potentials generated by action potentials of isolated frog sciatic nerves in a spherical volume.

Previous results in cylindrical volumes have shown that action potentials generate far-field potentials when experimental conditions are such that quadrupolar components of the action potential are reduced to an equivalent dipole. We now show that the same conclusions are also reached within a spherical volume, again recording far-field potentials from isolated bullfrog nerves. A mathematical proof is given that shows that in a sphere, antipodal electrodes primarily detect far-field potentials from dipole generators and not quadrupole generators. A revised conception of the 'far-field' in evoked responses is discussed which equates far-field recordings with dipole detection.

Action Potentials

Action potentials in chick atria. Ontogenetic changes in the dependence of tetrodotoxin-resistant action potentials on calcium, strontium, barium.

Action potentials were recorded from chick embryo atrial muscle cells bathed in Tyrode's solution. Tetrodotoxin (TTX), 3.1 muM, was added to block the early, transient, Na+-dependent conductance system. Rectangular stimuli were used to evoke action potentials the peak amplitude (Ep) of which depend on the external concentration of divalent cations, [Me2+]0. The relationship between Ep and [Me2+]0 shifted to the right with increasing age. For example, the slope of Ep was 33 +/- 2,22 +/- 1 and 11 +/- 3 mV per 10-fold change in [Ca2+]0 on the 9th, 12th, and 18th incubation days, respectively. In solutions with reduced [Ca2+]0, Ep increased when Ba2+ or Sr2+ was added to the bath. The potency of Me2+ in generating action potentials was Ba2+ greater than Sr2+ greater than Ca2+ and this sequence did not change during development. Action potential amplitude, which was reduced in 18-day preparations, was increased by isoproterenol (increased Ca2+ conductance, gCa2+) and by tetraethylammonium (TEA) ion (decreased K+ conductance, gK). The results show that (1) Me2+-dependent action potentials support membrane excitation in chick atrial cells treated with TTX, and (2) the ability of Me2+ to support action potentials decreases during ontogenesis. We conclude from these experiments that the ontogenetically related decrease in Me2+-induced action potentials is the result of a reduction in gMe2+/gK+ during stimulation.

Action Potentials

Anemone toxin discriminates between ionic channels for receptor potential and for action potential production in a sensory neuron.

The effect of anemone toxin (ATX II), which slows sodium channel inactivation at electrically excitable membranes, was investigated in the slowly adapting stretch receptor organ of crayfish. The toxin affected the action potentials, but produced no changes in the stretch induced receptor potentials. This finding is further proof for the high selectivity of this toxin molecule for sodium channels which are gated by membrane depolarissations.

Action Potentials

Action potentials in single axons: effects of hyperbaric air and hydrostatic pressure.

Resting potential and action potential parameters of crayfish (Procambarus acutus) single axon were examined under hyperbaric air and hydrostatic pressure to 8.6 atmospheres absolute to determine if evidence for the basis of neurological dysfunctions that may occur in diving in this pressure range is detectable at the membrane level. Hyperbaric air increased the maximum rates of depolarization and repolarization of the action potential by (2.2 +/- 0.2) and (2.1 +/- 0.2)%/atm, respectively. Hydrostatic pressure had an opposite effect, decreasing the maximum rates of depolarization and repolarization by (0.57 +/- 0.13) and (0.9 +/- 0.3)%/atm, respectively. Action potential duration was decreased (0.91 +/- 0.19)%/atm by hyperbaric air. Action potential amplitude, resting potential, and threshold were unchanged by increasing pressure. Increasing the nitrogen tension alone produced results consistent with hyperbaric air compression. Thus, increased hydrostatic and nitrogen pressures oppositely affect the rates of polarization of the action potential in a reversible manner at pressures in the range encountered by human divers.

Action Potentials

Extracellular potentials related to intracellular action potentials during impulse conduction in anisotropic canine cardiac muscle.

This paper considers a quantitative description of intracellular and transmembrane currents in anisotropic muscle, with emphasis on the factors that determine the extracellular potentials. Although Vmax of the intracellular action potential had no relation to changes in conduction velocity in anisotropic tissue with constant membrane properties, the extracellular waveforms were quite sensitive to velocity changes. Large amplitude biphasic deflection occurred in the fast areas, and in the slow areas the waveforms were of lower amplitude and triphasic in shape; i.e., negative potentials preceded the biphasic positive-negative deflection. The extracellular potentials were simulated on the bases of a model of intracellular currents, and the theoretical and measured results showed good agreement. In tissue with anisotropic conductivity, the relationship between the spatial intracellualr potential gradient and the magnitude of the extracellular potential of the excitation wave was opposite to the classical relationship in isotropic tissue. Due to the influence of the effective intracellular conductivity on the spread of intracellular currents and on conduction velocity, in anisotropic tissue the extracellular potential decreased as the intracellular potential gradient increased. The peak values of the positive and negative potentials and the spatial distribution of the potential gradients varied considerably along the activation front. These findings were accounted for by differences in the distribution and spatial extent of the transmembrane currents, which were determined by the intracellular currents. The theoretical analysis showed that intracellular and transmembrane currents were proportional to the local conduction velocities of the wavefront. Thereby, it was not possible to have a "uniform layer" of current when there were differences in conduction velocity along the length of the excitation wave. The implications of the analysis are considerable, since the gratifying agreement between the theoretical and measured results indicates that the details of the extracellular waveforms can be explained on the basis of the distribution of intracellular currents; i.e., extracellular potentials provide a sensitive index of intracellular current flow.

Action Potentials

An analysis of the effect of the rate of stimulation and adrenaline on the duration of the cardiac action potential.

1. Changes of action potential duration in cat papillary muscle have been correlated with changes of peak tension. It has been assumed that peak tension is an approximate indicator of [Ca2+]i. 2. When stimulation is commenced after a rest of several minutes, or after a decrease or increase of the stimulus rate, or after rest periods of different duration the changes of action potential duration are closely related to changes of peak tension. These results suggest that [Ca2+]i is of primary importance in determining rate-dependent changes of action potential duration, including the shortening of the action potential at high rates of stimulation. 3. The results also indicate the presence of a factor which tends to prolong the action potential at high rates of stimulation. Thus the duration of the action potential at high stimulus rates is longer than at lower rates when measured at a given value of peak tension. Furthermore in low Ca2+ there can be a prolongation of the steady state action potential at high rates. Comparison with the work of Cohen et al. (1976) suggests that this factor is responsible for the polarity of the T-wave of the ECG. 4. The action of adrenaline on action potential duration has also been analysed. It is shown to have two effects--a prolonging effect probably related to the adrenaline induced increase of Isi, and a shortening effect probably related to an increase of [Ca2+]i (as judged by the increase of peak tension).

Action Potentials