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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.

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Summating potential-action potential waveform amplitude and width in the diagnosis of Menière's disease.

OBJECTIVES: It has been suggested that analyzing the width and amplitude of the summating potential-action potential (SP-AP) waveforms can increase the sensitivity of electrocochleography. The objective of this study was to evaluate the ratio of SP to AP amplitude (SP/AP) and SP-AP waveform width, as well as the AP latency difference to condensation and rarefaction clicks, for the diagnosis of Menière's disease. STUDY DESIGN: This was a prospective, controlled study. METHODS: We used transtympanic electrocochleography to evaluate 21 patients with definite Menière's disease and 19 normal-hearing patients with other cochleovestibular disorders, comparing SP/AP, AP latency difference, and SP-AP waveform widths as well as calculating the diagnostic sensitivity of these parameters. RESULTS: Mean SP-AP waveform width was 1.89 ms in the study group and 1.58 ms in the control group. Mean SP/AP was 0.37 in the study group and 0.22 in the control group. The mean product of SP-AP waveform width and SP/AP was 75.26 ms% in the study group and 34.60 ms% in the control group. Mean AP latency difference was 0.13 ms in the study group and 0.07 ms in the control group. For the parameters evaluated, the differences between the groups were statistically significant. In the study group, the sensitivities for the width of the SP-AP waveform, the SP/AP, and the AP latency difference were 33.3%, 52.4%, and 23.8%, respectively. CONCLUSIONS: The use of the parameters evaluated did not increase the sensitivity of the electrocochleography, whether used in isolation or in conjunction with the SP/AP. Determining SP/AP presented the greatest sensitivity.

Action Potentials↗

The parallelism between the action potential, action current, and membrane resistance at a node of Ranvier.

1. Simultaneous measurements of action potential and resistance and of action current and impedance change have been made at a single node of Ranvier. 2. There is a parallelism between action potential, action current, and resistance change measured at a node of Ranvier. 3. Some implications of these results have been discussed in relation to the corresponding data obtained from the squid giant axon.

Action Potentials↗

Simultaneous recording of atrial and ventricular monophasic action potentials: monophasic action potential duration during atrial pacing, ventricular pacing, and ventricular fibrillation.

A newly developed transvenous suction electrode was used in dogs to record monophasic action potentials (MAPs) from the right atrium and right ventricle simultaneously. Continuous MAP recordings could be made from the same endocardial site for test periods of 1.5 hours. Left ventricular pacing at increasing heart rates resulted in a statistically significant decrease of right ventricular MAP duration. A high degree of correlation was found between right ventricular MAP duration at 90% of repolarization and the QT interval during both right atrial and left ventricular pacing. At the onset of ventricular fibrillation (VF), right ventricular MAP duration shortened to 25% of the value obtained during left ventricular pacing at a cycle length of 250 ms. A cyclic alternation in amplitude of the right ventricular MAPs was observed during VF. Fast Fourier Transform Analysis of right ventricular MAPs during VF showed a significant dominant frequency at 12 Hz, with no levels of interest beyond this frequency. This observation might prove to be useful in elaborating a new algorithm for the automatic detection of ventricular fibrillation.

Action Potentials↗

Postnatal maturation of rat hypothalamoneurohypophysial neurons: evidence for a developmental decrease in calcium entry during action potentials.

Action potentials and voltage-gated currents were studied in acutely dissociated neurosecretory cells from the rat supraoptic nucleus during the first three postnatal weeks (PW1-PW3), a period corresponding to the final establishment of neuroendocrine relationships. Action potential duration (at half maximum) decreased from 2.7 to 1.8 ms; this was attributable to a decrease in decay time. Application of cadmium (250 microM) reduced the decay time by 43% at PW1 and 21% at PW3, indicating that the contribution of calcium currents to action potentials decreased during postnatal development. The density of high-voltage-activated calcium currents increased from 4.4 to 10.1 pA/pF at postnatal days 1-5 and 11-14, respectively. The conductance density of sustained potassium current, measured at +20 mV, increased from 0.35 (PW1) to 0.53 (PW3) nS/pF. The time to half-maximal amplitude did not change. Conductance density and time- and voltage-dependent inactivation of the transient potassium current were stable from birth. At PW1, the density and time constant of decay (measured at 0 mV) were 0.29 nS/pF (n = 12) and 17.9 ms (n = 10), respectively. Voltage-dependent properties and density (1.1 nS/pF) of the sodium current did not change postnatally. During PW1, fitting the mean activation data with a Boltzmann function gave a half-activation potential of -25 mV. A double Boltzman equation was necessary to adequately fit the inactivation data, suggesting the presence of two populations of sodium channels. One population accounted for approximately 14% of the channels, with a half-inactivation potential of -86 mV; the remaining population showed a half-inactivation potential of -51 mV. A mathematical model, based on Hodgkin-Huxley equations, was used to assess the respective contributions of individual currents to the action potential. When the densities of calcium and sustained potassium currents were changed from immature to mature values, the decay time of the action potentials generated with the model decreased from 2.85 to 1.95 ms. A similar reduction was obtained when only the density of the potassium current was increased. Integration of the calcium currents generated during mature and immature action potentials demonstrated a significant decrease in calcium entry during development. We conclude that the developmental reduction of the action potential duration 1) is a consequence of the developmentally regulated increase in a sustained potassium current and 2) leads to a reduction of the participation of calcium currents in the action potential, resulting in a decreased amount of calcium entering the cell during each action potential.

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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.

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Junction potentials and action potentials of the crayfish myocardium.

INTRODUCTION: The purpose of this investigation was to study the properties of junction and action potentials elicited by nerve stimulation in the absence of the cardiac ganglion in crayfish myocardium. METHODS AND RESULTS: The cardiac ganglion was surgically removed in isolated crayfish hearts. Electrical stimulation of one of the peripheral anterolateral nerves provided isolated junction potentials and action potentials free of the usual postspike bursts of junction potentials. The single junction potentials displayed amplitudes of up to 25 mV and slow exponential decay; the mean time constant was 170 +/- 13 msec (approximately x +/- SD). In fully recovered tissue, the junction potentials triggered action potentials free of repetitive subthreshold discharges. Tetrodotoxin did not alter the amplitude or shape of action potentials initiated by direct electrical stimulation of the muscle cells. Calcium channel blocking agents such as Cd2+ and Ni2+ eliminated the action potentials but not the junction potentials. Tetraethylammonium markedly prolonged the action potential duration. CONCLUSIONS: Our data suggest that: (1) A slow decay of the junction potentials may result from the disappearance of the neurotransmitter; this process also accounts for the late slow repolarization of the final part of the action potentials; (2) The equilibrium potential of the junction potentials is close to 0 mV; (3) The upstroke of the action potentials is carried by calcium currents; (4) The fast repolarization phase of the action potentials is likely caused by the delayed rectifier; and (5) The refractory phase outlasts the duration of the action potential.

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Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials.

Action potentials in juvenile and adult rat layer-5 neocortical pyramidal neurons can be initiated at both axonal and distal sites of the apical dendrite. However, little is known about the interaction between these two initiation sites. Here, we report that layer 5 pyramidal neurons are very sensitive to a critical frequency of back-propagating action potentials varying between 60 and 200 Hz in different neurons. Bursts of four to five back-propagating action potentials above the critical frequency elicited large regenerative potentials in the distal dendritic initiation zone. The critical frequency had a very narrow range (10-20 Hz), and the dendritic regenerative activity led to further depolarization at the soma. The dendritic frequency sensitivity was suppressed by blockers of voltage-gated calcium channels, and also by synaptically mediated inhibition. Calcium-fluorescence imaging revealed that the site of largest transient increase in intracellular calcium above the critical frequency was located 400-700 micrometer from the soma at the site for initiation of calcium action potentials. Thus, the distal dendritic initiation zone can interact with the axonal initiation zone, even when inputs to the neuron are restricted to regions close to the soma, if the output of the neuron exceeds a critical frequency.

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Abnormal development of kitten retino-geniculate connectivity in the absence of action potentials.

Action potentials were silenced in one eye of neonatal kittens by repeated intraocular injections of tetrodotoxin for 5 to 8 weeks. After tetrodotoxin blockade was allowed to wear off, receptive field properties of individual relay cells in the lateral geniculate nucleus were examined. The many ON-OFF and binocular fields found in the layers that receive input from the treated eye suggest that these cells had extremely abnormal retino-geniculate synaptic connections. These effects were different in kind from those seen after deprivation rearing that does not silence action potentials. Lack of action potential activity was concluded to lead to abnormal development in the central nervous system.

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A context-free data compression approach to measuring information transmission by action potentials.

Action potentials allow nervous systems to transmit information rapidly and efficiently over considerable distances, but what is the information they carry and how much can be carried by one neuron? Often, qualitative and vague descriptions are used, such as the firing rate representing intensity. Recent attempts to quantify information transmission by action potentials have concentrated on treating neurons as communication channels, whose information capacity can be estimated from their signal-to-noise ratios. However, this only indicates how much information could theoretically be carried, not the actual amount at any given time, and the ratio itself depends on assumptions about information coding. Here we introduce a different approach based on the concept of data compression, which has become familiar with the widespread use of digital computers and networks. Compression takes advantage of redundancy in a sequence of numbers to reduce its size, but allows it to be reconstructed later without error. We show that data compression by a context-free grammar can quantitatively estimate the real information content of action potential signals without any prior assumptions about coding, or knowledge of neural inputs. Measurements of information coding by mechanosensory neurons are used as examples, but a major advantage of this approach is its generality. It can estimate information transmission by any neuron whose output can be measured, regardless of neuronal type, connectivity or function.

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Ionic basis of the resting membrane potential and action potential in the pharyngeal muscle of Caenorhabditis elegans.

The pharynx of C. elegans is a rhythmically active muscle that pumps bacteria into the gut of the nematode. This activity is maintained by action potentials, which qualitatively bear a resemblance to vertebrate cardiac action potentials. Here, the ionic basis of the resting membrane potential and pharyngeal action potential has been characterized using intracellular recording techniques. The resting membrane potential is largely determined by a K(+) permeability, and a ouabain-sensitive, electrogenic pump. As previously suggested, the action potential is at least partly dependent on voltage-gated Ca(2+) channels, as the amplitude was increased as extracellular Ca(2+) was increased, and decreased by L-type Ca(2+) channel blockers verapamil and nifedipine. Barium caused a marked prolongation of action potential duration, suggesting that a calcium-activated K(+) current may contribute to repolarization. Most notably, however, we found that action potentials were abolished in the absence of external Na(+). This may be due, at least in part, to a Na(+)-dependent pacemaker potential. In addition, the persistence of action potentials in nominally free Ca(2+), the inhibition by Na(+) channel blockers procaine and quinidine, and the increase in action potential frequency caused by veratridine, a toxin that alters activation of voltage-gated Na(+) channels, point to the involvement of a voltage-gated Na(+) current. Voltage-clamp analysis is required for detailed characterization of this current, and this is in progress. Nonetheless, these observations are quite surprising in view of the lack of any obvious candidate genes for voltage-gated Na(+) channels in the C. elegans genome. It would therefore be informative to re-evaluate the data from these homology searches, with the aim of identifying the gene(s) conferring this Na(+), quinidine, and veratridine sensitivity to the pharynx.

4-Aminopyridine↗

[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.

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Investigation of the mechanism by which ketanserin prolongs the duration of the cardiac action potential.

Action potential duration (APD) lengthening is believed to underlie the cardiac arrhythmogenicity of ketanserin, a serotonin (5-HT)2A/2C receptor antagonist. We wished to determine (a) whether this activity involves blockade of 5-HT2A/2C receptors and (b) the precise mechanism of ketanserin-induced APD prolongation. APs were recorded in guinea pig isolated papillary muscles by conventional "floating" microelectrodes, and potassium currents in guinea pig isolated myocytes were recorded in the whole-cell configuration. Ketanserin (1-10 microM) increased APD (EC50 value for enhancing APD at 90% repolarization (APD90) 3.1 +/- 2.7 microM, n = 24), without affecting resting potential, maximum upstroke velocity (Vmax) or AP amplitude (APA). Pirenperone (10 microM), a ketanserin congener, similarly increased APD90 from 204 +/- 3 to 241 +/- 7 ms (p < 0.001, n = 6). No increase in APD was observed, however, with ritanserin or ICI 170809, even at high concentrations (10 microM, n = 6, respectively), two 5-HT2A/2C receptor antagonists chemically distinct from ketanserin, thereby excluding the involvement of 5-HT2A/2C receptors in mediating APD lengthening. That APD prolongation was mediated specifically by the benzolyl-piperidine moiety of ketanserin and pirenperone was confirmed by 1-propyl-4(4-fluorobenzoyl)piperidine (PFBP), which evoked APD lengthening effects remarkably similar to those produced by ketanserin and pirenperone (EC50 3.73 +/- 2.6 microM, n = 12). In isolated cardiomyocytes, ketanserin (1-32 microM) selectively and concentration-dependently reduced the IKr component of the delayed outward current (IK) without affecting the inward rectifier current, IK1. Thus, ketanserin (32 microM) significantly reduced IK at a potential value of -20 mV from 813 +/- 65 to 569 +/- 55 pA (p < 0.001, n = 6), whereas at a potential value of -110 mV, IK1 was not significantly affected (730 +/- 103 vs. 603 +/- 143 pA, respectively; n=6). The results demonstrate that APD is prolonged by ketanserin and congeners but not be chemically different 5-HT2A/2C receptor antagonists. The benzoyl-piperidine moiety appears to mediate the APD-prolonging effects of ketanserin and pirenperone specifically. Furthermore, ketanserin-induced APD lengthening does not appear to involve 5-HT2A/2C receptors but is consecutive to direct blockade of myocardial potassium channels.

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.

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