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Contribution of a swelling-activated chloride current to changes in the cardiac action potential.

The purpose of this investigation was to determine to what extent the swelling-activated Cl- current (ICl,swell) contributes to swelling-induced changes in the resting membrane potential and action potential duration (APD) in ventricular myocytes. Action potentials were recorded from guinea pig ventricular myocytes using conventional whole cell recording techniques. Cell swelling caused initial lengthening followed by a variable shortening of APD. In 59% of cells this secondary APD shortening had a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive component, consistent with a contribution from ICl,swell. Furthermore, DIDS partially antagonized the depolarization of the resting membrane potential that occurred during cell swelling. We have modeled the ICl,swell using the Oxsoft Heart computer program. Action potential changes predicted by the model agree well with the observed DIDS-sensitive component of the change in the action potential during cell swelling. We conclude that activation of ICl,swell contributes to shortening of APD and depolarization of the resting membrane potential during cell swelling in cardiac myocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Influence of Na/Ca exchange stoichiometry on model cardiac action potentials.

Cardiac action potential simulations were done with the stoichiometry of the Na/Ca exchanger set a 4: 1. Using the Hilgemann-Noble (1987) model, this stoichiometry reduces the resting potential unless regulation by intracellular calcium is incorporated. The K(d) required for such regulation is consistent with current experimental estimates of this parameter.

Action Potentials↗

Conduction pattern of excitation in the amphibian atrium assessed by multiple-site optical recording of action potentials.

Spontaneous action potentials were monitored from multiple sites in the bullfrog atrium using a voltage-sensitive merocyanine-rhodanine dye together with a 100-element photodiode matrix array, and we have assessed the spread of the excitation from the pacemaker. Isochrone curves of conduction were obtained by timing the initiation of the action potential-related optical signals: we constructed maps of the spread. Excitatory waves appeared to conduct radially from the pacemaking area over the atrium, and the conduction velocity in the left atrium exceeded that in the right atrium.

Animals↗

Underestimation of auditory fatigue as measured by the compound action potential.

The action potential (AP), summating potential (SP), and cochlear microphonic (CM) were measured in rats in response either to clicks or pure tones prior to and following 3 min of exposure to pure tones at a level 5 db less than that which produced maximum CM. The ratio, in decibels, between pre-exposure and post-exposure potentials, for the same exposure and probe stimulus parameters, was taken as an index of decrement. The relative reduction in voltage resulting from the exposure was greater for the SP than for the AP when these potentials were elicited with 20-msec probe tone bursts between 70-80 db SPL having instantaneous rise times. However, for weaker probe levels within 20 db of that yielding AP potentials of 1 mu V, the AP and SP bpth exhibited similar losses. The CM and the click-evoked AP showed essentially no decrement. These results suggest that the SP might be a better indicator of noise-induced auditory decrement (fatigue?) than the CM. Theories of central auditory fatigue may be based on incorrect interpretations of previously published data obtained from cochlear and neural recordings.

Action Potentials↗

Distributed computing for membrane-based modeling of action potential propagation.

Action potential propagation simulations with physiologic membrane currents and macroscopic tissue dimensions are computationally expensive. We, therefore, analyzed distributed computing schemes to reduce execution time in workstation clusters by parallelizing solutions with message passing. Four schemes were considered in two-dimensional monodomain simulations with the Beeler-Reuter membrane equations. Parallel speedups measured with each scheme were compared to theoretical speedups, recognizing the relationship between speedup and code portions that executed serially. A data decomposition scheme based on total ionic current provided the best performance. Analysis of communication latencies in that scheme led to a load-balancing algorithm in which measured speedups at 89 +/- 2% and 75 +/- 8% of theoretical speedups were achieved in homogeneous and heterogeneous clusters of workstations. Speedups in this scheme with the Luo-Rudy dynamic membrane equations exceeded 3.0 with eight distributed workstations. Cluster speedups were comparable to those measured during parallel execution on a shared memory machine.

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↗

A quantitative evaluation of the magnetic field generated by a CA3 pyramidal cell at EPSP and action potential stages.

We evaluate quantitatively which behavioral stage dominantly generates magnetic field adjacent to a CA3 pyramidal cell by using a compartmental model with dendrites and an axon. Generally speaking, there are four stages in the potential behavior, i.e., excitatory and inhibitory postsynaptic potential, firing action potential, bursting action potential, if any, and after hyperpolarization potential stages. Calculated magnetic field also consists of corresponding four stages. We find, first, the dominant origin of the peaks of the magnetic field is counter propagating pulses at the firing and bursting stage at basal and apical dendrites. Second, the amplitude of the magnetic field changes to a great extent by the cancellation timing of the apical- and basal-originating fields depending on the calcium ionic channel spikes. Third, the field generated by the current flowing through the axon is significant enough when the temporal resolution of the measurement system becomes high. The results predict that the magnetic-field waveform measured in physiological experiments represents the dendritic configurations, channel density distributions, and bursting characteristics. These facts enable new investigations of neuronal activities in more detail through the observation of the magnetic-field waveform.

Action Potentials↗

Potentiation of sural nerve Abeta action potential after neurogenic inflammation.

Inflammatory mediators modulate voltage-gated sodium channels through protein kinase-mediated pathways. However, it is not clear whether neurogenic inflammation may also alter the properties of distantly located channels along axon shafts supplying the inflamed dermatome. In this study, localized inflammation was induced via intradermal injection of capsaicin within the receptive field of the sural nerve, and compound action potentials (CAP) evoked by sural nerve stimulation were recorded from the sciatic nerve proximally. The area measured under the A beta CAP increased significantly within 5 min after capsaicin injection. Distal injection of lidocaine at the ankle division of the sural nerve prior to capsaicin injection reversed this increase. In addition, application of a lipophilic protein kinase inhibitor H7 (100 microM) through a perfusion chamber placed on the sciatic nerve also reversed this increase. Our results suggest that during neurogenic inflammation, action potential activity is increased, triggering activation of protein kinases that may rapidly alter membrane conductance to potentiate action potential propagation along peripheral nerves.

Action Potentials↗

[An experimental study on conductive spinal cord action potentials evoked by direct stimulation of the spinal cord--pathway and source of conductive action potentials in the spinal cord].

The following experiments were carried out in adult cats to clarify the pathway and origin of the conductive spinal cord action potential evoked by dorsal epidural stimulation. (1) Comparison with the potential by surface stimulation of the spinal cord: Since waveforms, conduction velocity, and the relationships between the stimulation site and the change in threshold level were equal to those of surface stimulation, epidural stimulation and direct surface stimulation apparently induced the potential deriving from the same origin. (2) Recording of single fiber action potential: The mean conduction velocity of the dorsal column fiber was approximately 50 m/sec and that of the dorsolateral funiculus fiber was about 80 m/sec. 15-20% of potential N1 and 80-85% of potentials N2 and N3 were composed by the dorsal column fibers, whereas 80-85% of N1 and 15-20% of N2 and N3 were composed by the dorsolateral funiculus fibers.

Animals↗

Altered diaphragm muscle action potentials in Zucker diabetic fatty (ZDF) rats.

The Zucker diabetic fatty (ZDF) rat is a model of type 2 diabetes, being characterized by obesity, diabetes, and dyslipidemia. In vitro studies tested the hypothesis that diaphragm muscle from ZDF rats has abnormal resting membrane potential and action potentials, similar to type 1 diabetic rodents. Resting membrane potential was comparable for muscle from ZDF and control rats. Diaphragm from ZDF rats had augmented action potential peak height (92.1 mV versus 82.4 mV, P<0.00001), overshoot (15.6 mV versus 8.1 mV, P<0.001) and area (80.7 mV ms versus 68.6 mV ms, P<0.001) compared with that from controls. Action potential rate of depolarization and repolarization were not affected. The K(+) blocker, 3,4-diaminopyridine, augmented action potential duration and area of muscle from ZDF and controls, but without significant differences between animal groups. These findings in ZDF rats contrast with type 1 diabetic rats, suggesting that isolated hyperglycemia differs from hyperglycemia combined with other metabolic perturbations with respect to diaphragm electrophysiological derangements.

Action Potentials↗

Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential.

1. The action potential clamp technique was exploited to evaluate the rate dependency of delayed rectifier currents (I(Kr) and I(Ks)) during physiological electrical activity. I(Kr) and I(Ks) were measured in guinea-pig ventricular myocytes at pacing cycle lengths (CL) of 1000 and 250 ms. 2. A shorter CL, with the attendant changes in action potential shape, was associated with earlier activation and increased magnitude of both I(Kr) and I(Ks). Nonetheless, the relative contributions of I(Kr) and I(Ks) to total transmembrane current were independent of CL. 3. Shortening of diastolic interval only (constant action potential shape) enhanced I(Ks), but not I(Kr). 4. I(Kr) was increased by a change in the action potential shape only (constant diastolic interval). 5. In ramp clamp experiments, I(Kr) amplitude was directly proportional to repolarization rate at values within the low physiological range (< 1.0 V s(-1)); at higher repolarization rates proportionality became shallower and finally reversed. 6. When action potential duration (APD) was modulated by constant current injection (I-clamp), repolarization rates > 1.0 V s(-1) were associated with a reduced effect of I(Kr) block on APD. The effect of changes in repolarization rate was independent of CL and occurred in the presence of I(Ks) blockade. 7. In spite of its complexity, the behaviour of I(Kr) was accurately predicted by a numerical model based entirely on known kinetic properties of the current. 8. Both I(Kr) and I(Ks) may be increased at fast heart rates, but this may occur through completely different mechanisms. The mechanisms identified are such as to contribute to abnormal rate dependency of repolarization in prolonged repolarization syndromes.

Action Potentials↗