Role of High-Voltage Activated Potassium Currents in High-Frequency Neuronal Firing: Evidence From a Basal Metazoan

2002 ◽  
Vol 88 (2) ◽  
pp. 861-868 ◽  
Author(s):  
Steven D. Buckingham ◽  
Andrew N. Spencer

Certain neurons of vertebrates are specialized for high-frequency firing. Interestingly, high-frequency firing is also seen in central neurons in basal bilateral metazoans. Recently, the role of potassium currents with rightward-shifted activation curves in producing high-frequency firing has come under scrutiny. We apply intracellular recording, patch-clamp techniques, and compartmental modeling to examine the roles of rightward-shifted potassium currents in repetitive firing and shaping of action potentials in central neurons of the flatworm, Notoplana atomata ( Phylum Platyhelminthes). The kinetic properties of potassium and sodium currents were determined from patch-clamp experiments on dissociated brain cells. To predict the effects of changing the steady-state and kinetic properties of these potassium currents, these data were incorporated into a computer model of a 30-μm spherical cell with the levels of current adjusted to approximate the values recorded in voltage-clamp experiments. The model was able to support regenerative spikes at high frequencies in response to injected current. Current-clamp recordings of cultured cells and of neurons in situ also showed evidence of very-high-frequency firing. Adjusting the ratio of inactivating to non-inactivating potassium currents had little effect upon the firing pattern of the cell or its ability to fire at high frequencies, whereas the presence of the non-inactivating current was necessary for repetitive firing. Computer simulations suggested that the rightward shift in voltage sensitivity confers a raised firing threshold, while rapid channel kinetics underlie high frequency firing, and the large activation range enhances the coding range of the cell.

2020 ◽  
Vol 132 (1) ◽  
pp. 148-160
Author(s):  
F G Duque ◽  
C A Rodriguez-Saltos ◽  
M F Monteros ◽  
W Wilczynski

Abstract Some species of Andean hummingbirds produce high-frequency vocalizations which exceed the vocal range of most birds. They also challenge our understanding of the role of habitat structure in the evolution of vocal signals because these hummingbirds live in strikingly different habitats, ranging from cloud forest to high-altitude grasslands. Although these vocalizations are produced at high frequencies, they exhibit considerable variation in frequency content and temporal structure. The calls of the hummingbirds from the cloud forest are simpler and have a narrow frequency range compared to the complex song of the grasslands hummingbird. We hypothesized that each of the three high-frequency vocalizations is adapted for transmission in their habitat. We characterized the transmission of high-frequency vocal signals in the cloud forest and in the grasslands. All vocalizations attenuated and degraded substantially at short distances, suggesting that they are adapted for short-range communication. The simple vocalizations of the cloud-forest species transmitted better in both environments compared to the complex song of the grasslands hummingbird, probably due to relaxed constraints for high-frequency sounds in open habitats.


1955 ◽  
Vol 33 (1) ◽  
pp. 695-723
Author(s):  
William D. Wilkey ◽  
Frederick R. Miller

Observations were made on rabbits and cats under dial anesthesia. Monopolar recording from cortex was used. Strychnine, 1%, on motor cerebral cortex is excitatory, as shown by increased firing of motor units; later the strychnine induces cortical spikes. Each spike is triphasic, consisting of an initial, small positive wave, a large, fast negative wave, and a final, slow positive wave; the first two waves are believed to be excitomotor; the final positive wave is regarded as a positive after-potential with relative quiescence of neurons; it is not excitatory for motor units. Microwaves at high frequency occur during first positive wave and ascent of negative wave; microwaves decay during descent of negative wave and are absent during final positive wave. Microwaves are caused by fast, repetitive firing of neurons; this neuronal firing causes excitation of motor units. Intracortical and extracortical conduction are believed to be repetitive. Acetylcholine (ACh), 1%, on eserinized cortex induces triphasic spikes, resembling those from strychnine; microwaves are likewise present. Strychnine, eserine, and ACh are believed to stimulate cortical synapses. Strychnine and ACh, though very different chemically, are believed to trigger the same fundamental cortical mechanism of conduction.


1955 ◽  
Vol 33 (4) ◽  
pp. 695-723
Author(s):  
William D. Wilkey ◽  
Frederick R. Miller

Observations were made on rabbits and cats under dial anesthesia. Monopolar recording from cortex was used. Strychnine, 1%, on motor cerebral cortex is excitatory, as shown by increased firing of motor units; later the strychnine induces cortical spikes. Each spike is triphasic, consisting of an initial, small positive wave, a large, fast negative wave, and a final, slow positive wave; the first two waves are believed to be excitomotor; the final positive wave is regarded as a positive after-potential with relative quiescence of neurons; it is not excitatory for motor units. Microwaves at high frequency occur during first positive wave and ascent of negative wave; microwaves decay during descent of negative wave and are absent during final positive wave. Microwaves are caused by fast, repetitive firing of neurons; this neuronal firing causes excitation of motor units. Intracortical and extracortical conduction are believed to be repetitive. Acetylcholine (ACh), 1%, on eserinized cortex induces triphasic spikes, resembling those from strychnine; microwaves are likewise present. Strychnine, eserine, and ACh are believed to stimulate cortical synapses. Strychnine and ACh, though very different chemically, are believed to trigger the same fundamental cortical mechanism of conduction.


2003 ◽  
Vol 121 (6) ◽  
pp. 529-540 ◽  
Author(s):  
Karel Talavera ◽  
Annelies Janssens ◽  
Norbert Klugbauer ◽  
Guy Droogmans ◽  
Bernd Nilius

The selectivity filter of all known T-type Ca2+ channels is built by an arrangement of two glutamate and two aspartate residues, each one located in the P-loops of domains I–IV of the α1 subunit (EEDD locus). The mutations of the aspartate residues to glutamate induce changes in the conduction properties, enhance Cd2+ and proton affinities, and modify the activation curve of the channel. Here we further analyze the role of the selectivity filter in the gating mechanisms of T-type channels by comparing the kinetic properties of the α1G subunit (CaV3.1) to those of pore mutants containing aspartate-to-glutamate substitution in domains III (EEED) or IV (EEDE). The change of the extracellular pH induced similar effects on the activation properties of α1G and both pore mutants, indicating that the larger affinity of the mutant channels for protons is not the cause of the gating modifications. Both mutants showed alterations in several gating properties with respect to α1G, i.e., faster macroscopic inactivation in the voltage range from −10 to 50 mV, positive voltage shift and decrease in the voltage sensitivity of the time constants of activation and deactivation, decrease of the voltage sensitivity of the steady-state inactivation, and faster recovery from inactivation for long repolarization periods. Kinetic modeling suggests that aspartate-to-glutamate mutations in the EEDD locus of α1G modify the movement of the gating charges and alter the rate of several gating transitions. These changes are independent of the alterations of the selectivity properties and channel protonation.


2002 ◽  
Vol 87 (1) ◽  
pp. 87-102 ◽  
Author(s):  
Raimondo D'Ambrosio ◽  
David S. Gordon ◽  
H. Richard Winn

Little information is available on the specific roles of different cellular mechanisms involved in extracellular K+ homeostasis during neuronal activity in situ. These studies have been hampered by the lack of an adequate experimental paradigm able to separate K+-buffering activity from the superimposed extrusion of K+ from variably active neurons. We have devised a new protocol that allows for such an analysis. We used paired field- and K+-selective microelectrode recordings from CA3 stratum pyramidale during maximal Schaffer collateral stimulation in the presence of excitatory synapse blockade to evoke purely antidromic spikes in CA3. Under these conditions of controlled neuronal firing, we studied the [K+]o baseline during 0.05 Hz stimulation, and the accumulation and rate of recovery of extracellular K+ at higher frequency stimulation (1–3 Hz). In the first set of experiments, we showed that neuronal hyperpolarization by extracellular application of ZD7288 (11 μM), a selective blocker of neuronal I hcurrents, does not affect the dynamics of extracellular K+. This indicates that the K+ dynamics evoked by controlled pyramidal cell firing do not depend on neuronal membrane potential, but only on the balance between K+ extruded by firing neurons and K+ buffered by neuronal and glial mechanisms. In the second set of experiments, we showed that di-hydro-ouabain (5 μM), a selective blocker of the Na+/K+-pump, yields an elevation of baseline [K+]o and abolishes the K+ recovery during higher frequency stimulation and its undershoot during the ensuing period. In the third set of experiments, we showed that Ba2+ (200 μM), a selective blocker of inwardly rectifying K+channels (KIR), does not affect the posttetanus rate of recovery of [K+]o, nor does it affect the rate of K+ recovery during high-frequency stimulation. It does, however, cause an elevation of baseline [K+]o and an increase in the amplitude of the ensuing undershoot. We show for the first time that it is possible to differentiate the specific roles of Na+/K+-pump and KIR channels in buffering extracellular K+. Neuronal and glial Na+/K+-pumps are involved in setting baseline [K+]o levels, determining the rate of its recovery during sustained high-frequency firing, and determining its postactivity undershoot. Conversely, glial KIR channels are involved in the regulation of baseline levels of K+, and in decreasing the amplitude of the postactivity [K+]oundershoot, but do not affect the rate of K+clearance during neuronal firing. The results presented provide new insights into the specific physiological role of glial KIR channels in extracellular K+ homeostasis.


2007 ◽  
pp. 807-813 ◽  
Author(s):  
H Haghdoust ◽  
M Janahmadi ◽  
G Behzadi

To understand the contribution of potassium (K+) channels, particularly alpha-dendrotoxin (D-type)-sensitive K+ channels (Kv.1, Kv1.2 or Kv1.6 subunits), to the generation of neuronal spike output we must have detailed information of the functional role of these channels in the neuronal membrane. Conventional intracellular recording methods in current clamp mode were used to identify the role of alpha-dendrotoxin (alpha-DTX)-sensitive K+ channel currents in shaping the spike output and modulation of neuronal properties of cerebellar Purkinje neurons (PCs) in slices. Addition of alpha-DTX revealed that D-type K+ channels play an important role in the shaping of Purkinje neuronal firing behavior. Repetitive firing capability of PCs was increased following exposure to artificial cerebrospinal fluid (aCSF) containing alpha-DTX, so that in response to the injection of 0.6 nA depolarizing current pulse of 600 ms, the number of action potentials insignificantly increased from 15 in the presence of 4-AP to 29 action potentials per second after application of DTX following pretreatment with 4-AP. These results indicate that D-type K+ channels (Kv.1, Kv1.2 or Kv1.6 subunits) may contribute to the spike frequency adaptation in PCs. Our findings suggest that the activation of voltage-dependent K+ channels (D and A types) markedly affect the firing pattern of PCs.


2008 ◽  
Vol 100 (4) ◽  
pp. 1824-1834 ◽  
Author(s):  
Peng Zhang ◽  
Chun Yang ◽  
Rona J. Delay

Most odor responses in mouse vomeronasal neurons are mediated by the phospholipase C (PLC) pathway, activation of which elevates diacylglycerol (DAG). Lucas et al. showed that DAG activates transient receptor potential channels, subfamily C, member 2 (TRPC2), resulting in a depolarizing Ca2+ influx. DAG can be subsequently converted to arachidonic acid (AA) by a DAG lipase, the role of which remains largely unknown. In this study, we found that urine stimulation of vomeronasal neurons activated large-conductance Ca2+-activated K+ (BK) channels via AA production. Using isolated neurons, we demonstrated that repetitive applications of AA potentiated a K+ current that required a Ca2+ influx and was sensitive to specific BK blockers. Using immunocytochemistry, we found that BK channels are present in vomeronasal neurons with labeling on the soma and heavy labeling on the dendrite with a BK channel antibody. We examined the role of these BK channels in regulating neuronal firing when the neuron was activated by membrane depolarization or urine. Contrary to a recent report, our data suggest that BK channels contribute to adaptation of urine/odor responses because the inhibition of BK channels during urine stimulation promoted repetitive firing. These data strongly support the hypothesis that AA mediates an inhibitory pathway through BK channels, a possible mechanism for odor adaptation in vomeronasal neurons.


Author(s):  
R H. Selinfreund ◽  
A. H. Cornell-Bell

Cellular electrophysiological properties are normally monitored by standard patch clamp techniques . The combination of membrane potential dyes with time-lapse laser confocal microscopy provides a more direct, least destructive rapid method for monitoring changes in neuronal electrical activity. Using membrane potential dyes we found that spontaneous action potential firing can be detected using time-lapse confocal microscopy. Initially, patch clamp recording techniques were used to verify spontaneous electrical activity in GH4\C1 pituitary cells. It was found that serum depleted cells had reduced spontaneous electrical activity. Brief exposure to the serum derived growth factor, IGF-1, reconstituted electrical activity. We have examined the possibility of developing a rapid fluorescent assay to measure neuronal activity using membrane potential dyes. This neuronal regeneration assay has been adapted to run on a confocal microscope. Quantitative fluorescence is then used to measure a compounds ability to regenerate neuronal firing.The membrane potential dye di-8-ANEPPS was selected for these experiments. Di-8- ANEPPS is internalized slowly, has a high signal to noise ratio (40:1), has a linear fluorescent response to change in voltage.


2019 ◽  
Vol 85 (1(I)) ◽  
pp. 64-71 ◽  
Author(s):  
M. M. Gadenin

The cycle configuration at two-frequency loading regimes depends on the number of parameters including the absolute values of the frequencies and amplitudes of the low-frequency and high-frequency loads added during this mode, the ratio of their frequencies and amplitudes, as well as the phase shift between these harmonic components, the latter having a significant effect only with a small ratio of frequencies. Presence of such two-frequency regimes or service loading conditions for parts of machines and structures schematized by them can significantly reduce their endurance. Using the results of experimental studies of changes in the endurance of a two-frequency loading of specimens of cyclically stable, cyclically softened and cyclically hardened steels under rigid conditions we have shown that decrease in the endurance under the aforementioned conditions depends on the ratio of frequencies and amplitudes of operation low-frequency low-cycle and high-frequency vibration stresses, and, moreover, the higher the level of the ratios of amplitudes and frequencies of those stacked harmonic processes of loading the greater the effect. It is shown that estimation of such a decrease in the endurance compared to a single frequency loading equal in the total stress (strains) amplitudes can be carried out using an exponential expression coupling those endurances through a parameter (reduction factor) containing the ratio of frequencies and amplitudes of operation cyclic loads and characteristic of the material. The reduction is illustrated by a set of calculation-experimental curves on the corresponding diagrams for each of the considered types of materials and compared with the experimental data.


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