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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

Effects of AFD-21, a new class I antiarrhythmic agent, and AFD-19, its active metabolite, on the maximal rate of rise of action potentials in guinea pig papillary muscles: dependence on time, voltage, and action potential duration.

Effects of AFD-21 and AFD-19 (a new class I antiarrhythmic agent and its active metabolite, respectively) on the maximal rate of rise (Vmax) of action potentials (APs) were studied in guinea pig papillary muscles with special reference to their time, voltage, and action potential duration (APD) dependence. Both AFD-21 and AFD-19 (2-10 microM) reduced Vmax in a concentration-dependent manner without affecting the resting potential, APD, and effective refractory period. Both agents (5 microM) shifted the normalized Vmax resting potential curve (examined at 1 Hz) in the hyperpolarizing direction by 4-7 mV (voltage dependence). In addition, both agents (5 microM): a) caused a frequency-dependent reduction of Vmax at 0.25-3 Hz; b) developed a use-dependent (1 Hz) reduction of Vmax with an onset time constant of 1-3 s; and c) slowed the recovery process of Vmax, whose resultant recovery time constant was 2-3 s (time dependence). Nicorandil (1 mM), which shortens APD to about 25% of control, antagonized the AFD-21-induced time-dependent reductions of Vmax but not the AFD-19-induced reductions (APD dependence). These results suggest that the effects of AFD-21 on Vmax are APD dependent but those of AFD-19 are not, and thereby that AFD-21 and AFD-19 preferentially block inactivated and open sodium channels, respectively. The present findings are discussed from the viewpoint of the modulated or the guarded receptor hypothesis.

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

Latency and amplitude tuning curves of the N1 and N2 components of the cochlear nerve compound action potential.

Compound action potential tuning curves (CAP TCs) generated by masking the N1 component of the CAP provide a means of assessing the ability of the cochlea to selectively tune to certain stimuli. This paper examines some of the factors which can influence this TC when a moderately intense (i.e. 40-80 dB SPL) probe stimulus is used. At these levels, each of the four corners of the trapezoidal stimulus envelope is capable of generating a CAP. Also, short stimulus rise times can merge the CAPs produced by the first two corners, but this does not appear to have a major effect on the CAP TC. It was shown that the N2 component of the CAP for the first corner of the stimulus is equally capable of producing a well-tuned TC. Another study has shown that, in addition to amplitude decrements, one can use latency increases as a criterion for CAP TCs. We have demonstrated that latency TCs are more finely tuned than amplitude TCs at high levels, especially when the stimulus rise time is short.

Animals

Teaching field potentials: a microcomputer simulation of the nerve action potential in a bidimensional conductor.

A computer simulation of the extracellular field potential recording of nerve activity is presented. An experimental setup composed of an oscilloscope, a nerve, a conductive surface, and a recording electrode is graphically simulated. The user may study the influence of the position of the recording electrode and of certain nerve properties (membrane potential, velocity of conduction and action potential duration), on the action potential shape. The different waves which constitute the action potential may be analyzed and their peak values plotted as a function of the independent variable (e.g. electrode distance from the nerve). Three-dimensional plots of a set of action potentials as a function of the independent variable may also be obtained. The stimulation allows the user to study the basic factors which determine the configuration of an extracellularly recorded compound nerve action potential.

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

Mechanism of potentiation of contraction by depolarization during action potentials in guinea-pig ventricular muscle.

Action potentials were recorded from guinea-pig ventricular cells and contraction recorded by an optical technique. When the plateau of a single action potential was depolarized (by 70-120 pA applied 100 ms after the upstroke for 100 ms), contraction associated with the following normal action potential was potentiated. This potentiation was not seen in cells exposed to 10 mM-caffeine. The observations are consistent with potentiation of subsequent contraction by increased loading of caffeine-sensitive calcium stores, as a consequence of reduced Ca2+ extrusion or possibly Ca2+ entry via Na+-Ca2+ exchange during a depolarized plateau.

Action Potentials

Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential.

The properties of the autonomically regulated chloride current (ICl) were studied in isolated guinea pig ventricular myocytes. This current was elicited upon exposure to isoproterenol (ISO) and reversed upon concurrent exposure to acetylcholine (ACh). ICl was time independent and exhibited outward rectification. The responses to ISO and ACh could be blocked by propranolol and atropine, respectively, and ICl was also elicited by forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, and 3-isobutyl-l-methylxanthine, indicating that the current is regulated through a cAMP-dependent pathway. The reversal potential of the ISO-induced current followed the predicted chloride equilibrium potential, consistent with it being carried predominantly by Cl-. Activation of ICl produced changes in the resting membrane potential and action potential duration, which were Cl- gradient dependent. These results indicate that under physiological conditions ICl may play an important role in regulating action potential duration and resting membrane potential in mammalian cardiac myocytes.

Acetylcholine

Somatostatin blocks Ca2+ action potential activity in prolactin-secreting pituitary tumor cells through coordinate actions on K+ and Ca2+ conductances.

The hypothalamic peptide somatostatin (SRIF) suppresses secretory activity in phenotypically distinct pituitary endocrine cells. We have used tight-seal whole-cell recording techniques to study the peptide's effects on the electrical properties of tumor pituitary cells derived from rat (GH3/B6) and human adenomas that secrete human PRL in a SRIF-sensitive manner. Both cell types exhibited qualitatively similar electrophysiological properties and electrical responses to SRIF. Under the experimental conditions employed the majority of cells spontaneously generated Ca2+-dependent actions potentials. The actions of the peptide on cellular excitability were markedly affected by the presence of horse and fetal calf sera. Without these additives the electrical responses faded and could not be studied in detail. Therefore, recordings were conducted in media containing sera. In the presence of sera almost all cells spontaneously generated Ca2+ action potentials, and peptide-induced changes in excitability were well preserved. SRIF depressed spontaneous and evoked action potential activity in a dose-dependent manner at concentrations that reduced intracellular free calcium ([Ca2+]i) and suppressed basal PRL release. Current and voltage clamp experiments revealed coordinate actions of the peptide on excitable membrane properties. SRIF (1 nM) enhanced a depolarization-activated, rapidly inactivating outward K+ current, thereby effectively reducing the rate at which action potentials occurred. Over the 10-1000 nM range SRIF slowly activated a virtually noninactivating K+ conductance over a wide range of membrane potential. This effectively hyperpolarized cells away from the threshold for triggering Ca2+-dependent action potentials and shunted the membrane. The peptide induced K+ conductance activated at the level of the resting potential was progressively lost during the intracellular dialysis of whole-cell recording. Dilute aqueous lysates of cells included in the patch pipette prevented much of the rundown of this SRIF-induced electrical response while inclusion of an ATP-regenerating system preserved some of the peptide action. Over the 10-100 nM concentration range SRIF also reduced voltage-dependent Ca2+ current. Furthermore, pretreatment of cells with pertussis toxin abolished SRIF action on cellular excitability, suggesting that SRIF can regulate the function of ionic channels through GTP-binding proteins (G proteins). The results demonstrate that SRIF acts coordinately on the primary conductances expressed in tumor PRL cells to attenuate or block Ca2+ action potential generation and thus Ga2+ entry from extracellular sources.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Principal component analysis of the features of concentric needle EMG motor unit action potentials.

Motor unit action potentials (MUAPs) were recorded from the biceps muscle of normal subjects and of patients with nerve or muscle diseases. Principal component analysis of the MUAP amplitude, area, area/amplitude ratio, duration, and the number of turns and phases produced three components that among them contained 90% of the variance of the data set. Thus the dimensionality of data was reduced from six to three. The first component reflected changes in the size of the MU, whereas the second reflected variations in the arrival time at the recording electrode of the action potentials of muscle fibers in the motor unit. The third factor reflected local loss of muscle fibers within the MU territory. Patterns of variations in the three components were different in patients with neuropathy and myopathy.

Action Potentials

The recording of action potential currents as an assessment for drug actions on excitable cells.

The use of the cell-attached patch clamp configuration to record action potential currents is shown to have utility in the testing for drug actions on ion channels in excitable cell membrane. A patch pipette was used to isolate a small patch of cell membrane on cultured hippocampal or hypothalamic neurons and spontaneous R-C coupled action potential currents, with well-defined Na+ and K+ components, were recorded. The addition of several potassium channel-blocking drugs to the bath solution completely abolished the after-hyperpolarization phase of the action potential currents while preserving the sodium spike. These drugs have previously been shown to block a calcium-dependent potassium channel in cultured hippocampal neurons, a channel that is responsible for the late slow after-hyperpolarization macroscopic current recorded in these cells. The addition of tetrodotoxin to the bath solution eliminated the R-C coupled currents. The novel approach of using the recording of action potential currents to assess drug actions on ion channels would be expected to be applicable to a variety of excitable cells.

Action Potentials

Participation of slow inward current in the Purkinje fiber action potential overshoot.

We used microelectrode techniques to study the relationship of canine Purkinje fiber membrane potential and the action potential (AP) overshoot. At the maximum diastolic potential, -93.0 +/- 0.5 (SE) mV, AP overshoot was +37.7 +/- 0.4 mV. There was a range of membrane potentials (MP) less negative than the maximum diastolic potential from which action potentials were elicited with an overshoot greater than the control. Starting at an MP of less than -78.7 +/- 0.4 mV, AP overshoot was less than control. A maximum overshoot of +40.2 +/- 0.4 mV occurred at an MP of -85.4 +/- 0.4 mV. The relationship of the maximum upstroke velocity (Vmax) of phase 0 depolarization to MP was sigmoidal. Peak Vmax, 497 +/- 13 V/s, occurred at MP greater than or equal to -89.3 +/- 0.5 mV. The increase in overshoot was enhanced as perfusate [Ca2+] increased and decreased as [Ca2+] decreased. Slow-channel blocking agents and tetrodotoxin (TTX) depressed the peak of the curve relating overshoot to MP. TTX also decreased Vmax. The effect of TTX on overshoot but not on Vmax was reversed with Ca2+, 8.1 mM. The increase in overshoot for action potentials initiated during the terminal part of phase 3 was due to a slow, delayed component of the upstroke and appears to result from the slow inward current.

Action Potentials

[The effect of anesthetic agents on descending spinal cord evoked potential and the compound muscle action potentials elicited by stimulation at the cerebral motor cortex and the spinal cord].

Recently, intraoperative monitoring of the motor tract by descending spinal cord motor evoked potentials (MEP) and compound muscle action potentials (CMAP) has been applied in clinical testing. Since several reports have mentioned the vulnerability of these potentials to anesthetic agents, experimental studies were carried out on the relationship between these potentials and anesthesia using 41 adult cats. The effects of anesthesia on changes in amplitude of the direct wave (D wave) and indirect wave (I wave) of the MEP and CMAPs were investigated. These potentials were generated by stimulation of the spinal cord and the motor cortex, respectively. Enflurane (2%), halothane (1%) and isoflurane (1.5%) with pure oxygen decreased the amplitude of the I wave to less than 50% of the control level. The CMAP after stimulation of the spinal cord was degraded to less than 30%, and the CMAP after cortical stimulation vanished completely. Only the D wave was stable against inhalational anesthetic agents. Sixty-seven percent nitrous oxide with the above concentrations of these inhalational anesthetic agents decreased the amplitude of the I wave to less than 30% and the CMAP evoked by spinal cord stimulation vanished. The effect of modified NLA (diazepam and pentazocine) on these potentials was weaker than that of the inhalational anesthetic agents.

Action Potentials

Phase-plane analysis of action potentials in uterine smooth muscle.

Action potentials were recorded by microelectrode from narrow strips of pregnant rat uterus in vitro. The phase-plane display (V vs dV/dt) of selected action potentials was analysed by the method of Jenerick (1964) to yield the ionic current. From this membrane current data, various parameters of the action potential were calculated. In comparison to skeletal muscle action potentials, the ionic currents were 30-100 times smaller in the uterus action potential. Epinephrine hyperpolarized the resting potentials and suppressed spontaneous activity, but did not cause any significant changes in the stimulated action potential. The after-potential may have been affected by epinephrine, preventing repetitive firing, but the data were inconclusive. The phase-plane analysis results were similar to the results of the double sucrose gap voltage clamp method on the same tissue (Kao and McCullough, 1975).

Action Potentials