Differential Role of KIR Channel and Na+/K+-Pump in the Regulation of Extracellular K+ in Rat Hippocampus

2002 ◽  
Vol 87 (1) ◽  
pp. 87-102 ◽  
Author(s):  
Raimondo D'Ambrosio ◽  
David S. Gordon ◽  
H. Richard Winn
Keyword(s):  
High Frequency ◽  
Physiological Role ◽  
Neuronal Firing ◽  
Neuronal Membrane ◽  
High Frequency Stimulation ◽  
Kir Channels ◽  
Frequency Stimulation ◽  
Rate Of Recovery ◽  
Selective Blocker

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.

scholarly journals Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation

2021 ◽  
Author(s):  
Leon A Steiner ◽  
Andrea A Kuehn ◽  
Joerg RP Geiger ◽  
Henrik Alle ◽  
Milos Popovic ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
High Frequency ◽  
Symptomatic Relief ◽  
Neuronal Firing ◽  
High Frequency Stimulation ◽  
Inhibitory Input ◽  
Frequency Specificity ◽  
Evoked Field Potentials ◽  
Frequency Stimulation ◽  
Synaptic Dynamics

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr). Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for PD. Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode. Results: Excitatory and inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .007). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation, but not SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003). Interpretation: Persistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections.

Role of fascia in maintenance of muscle tension and pressure

1981 ◽  
Vol 51 (2) ◽  
pp. 317-320 ◽  
Author(s):  
S. R. Garfin ◽  
C. M. Tipton ◽  
S. J. Mubarak ◽  
S. L. Woo ◽  
A. R. Hargens ◽  
...  
Keyword(s):  
High Frequency ◽  
Muscle Tension ◽  
Fluid Pressure ◽  
Low Frequency ◽  
Testing Procedure ◽  
Force Transducer ◽  
High Frequency Stimulation ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation

The effect of fasciotomy on muscle tension (measured by a force transducer attached to the tendon) and interstitial fluid pressure (measured by Wick catheters in the muscle belly) was studied in the anterolateral compartments of 13 dog hindlimbs. Muscle tension and pressure were monitored in the tibialis cranialis muscle after low- and high-frequency stimulation of the peroneal nerve to produce twitch- and tetanic-type contractions. Fasciotomy decreased muscle force during the low-frequency stimulation by 16% (35.3 +/- 4.9 to 28.4 +/- 3.9 N) and during the high-frequency stimulation by 10% (60.8 %/- 4.9 to 54.8 +/- 3.9 N). Muscle pressure decreased 50% after fasciotomy under both conditions, 15 +/- 2 to 6 +/- 1 mmHg and 84 +/- 17 to 41 +/- 8 mmHg), respectively. Repeated functional evaluations during the testing procedure indicated that muscle fatigue was not a major factor in these results. It was concluded that fascia is important in the development of muscle tension and changes in interstitial pressure. Furthermore, the results raised questions concerning the merits of performing a fasciotomy for athletes with a compartment syndrome.

Rescue of motoneuron and muscle afferent function in cats by regeneration into skin. II. Ia-motoneuron synapse

1995 ◽  
Vol 73 (2) ◽  
pp. 662-673 ◽  
Author(s):  
L. M. Mendell ◽  
J. S. Taylor ◽  
R. D. Johnson ◽  
J. B. Munson
Keyword(s):  
High Frequency ◽  
Muscle Afferents ◽  
Medial Gastrocnemius ◽  
High Frequency Stimulation ◽  
Lateral Gastrocnemius ◽  
Essentially Normal ◽  
Muscle Afferent ◽  
Muscle Nerve ◽  
Frequency Stimulation

1. In this study we describe application of high-frequency stimulation to the group Ia afferent-to-motoneuron synapse of cats to determine the extent to which regeneration of axotomized muscle afferents and motoneurons into skin or into muscle rescues their ability to generate excitatory postsynaptic potentials (EPSPs). 2. The medial gastrocnemius (MG) muscle nerve was transected and 1) left chronically axotomized, 2) cross-united to the caudal cutaneous sural (CCS) nerve, or 3) self-united. The ability of the operated MG muscle afferents to generate EPSPs in normal lateral gastrocnemius-soleus (LGS) motoneurons and of normal LGS muscle afferents to generate EPSPs in the operated MG motoneurons was tested 5 wk-30 mo later. 3. EPSPs were generated by bursts of 32 shocks at 167 Hz and averaged in register. In normal cats, EPSP amplitude decreased (negative modulation) during these bursts in type S motoneurons and could increase or decrease in type F motoneurons (positive or negative modulation). 4. After axotomy, EPSPs generated both in axotomized motoneurons and by axotomized afferents showed only negative modulation during the burst, and the negative modulation was much greater than in normal animals. Regeneration of the muscle nerve into skin significantly decreased the negative modulation relative to axotomy. Regeneration of the muscle nerve into muscle restored the EPSP modulation behaviors even more, to essentially normal values. 5. We conclude that the ability of muscle afferents to generate EPSPs in motoneurons in response to high-frequency stimulation, and the ability of motoneurons to express those EPSPs, are both influenced by the target innervated by those neurons. Synaptic efficacy is severely reduced by target deprivation (axotomy), partially rescued by cross-regeneration into skin, and rescued virtually completely by regeneration into the native muscle. We speculate on the role of target-derived neurotrophins in these effects.

Frequency-dependent effects of electrical stimulation in the globus pallidus of dystonia patients

2012 ◽  
Vol 108 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Liu D. Liu ◽  
Ian A. Prescott ◽  
Jonathan O. Dostrovsky ◽  
Mojgan Hodaie ◽  
Andres M. Lozano ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
High Frequency ◽  
Gaba Release ◽  
Neuronal Firing ◽  
High Frequency Stimulation ◽  
Low Frequencies ◽  
Clinical Benefits ◽  
Frequency Stimulation ◽  
Train Length ◽  
Additional Support

Deep brain stimulation (DBS) in the globus pallidus internus (GPi) has been shown to improve dystonia, a movement disorder of repetitive twisting movements and postures. DBS at frequencies above 60 Hz improves dystonia, but the mechanisms underlying this frequency dependence are unclear. In patients undergoing dual-microelectrode mapping of the GPi, microstimulation has been shown to reduce neuronal firing, presumably due to synaptic GABA release. This study examined the effects of different microstimulation frequencies (1–100 Hz) and train length (0.5–20 s), with and without prior high-frequency stimulation (HFS) on neuronal firing and evoked field potentials (fEPs) in 13 dystonia patients. Pre-HFS, the average firing decreased as stimulation frequency increased and was silenced above 50 Hz. The average fEP amplitudes increased up to frequencies of 20–30 Hz but then declined and at 50 Hz, were only at 75% of baseline. In some cases, short latency fiber volleys and antidromic-like spikes were observed and followed high frequencies. Post-HFS, overall firing was reduced compared with pre-HFS, and the fEP amplitudes were enhanced at low frequencies, providing evidence of inhibitory synaptic plasticity in the GPi. In a patient with DBS electrodes already implanted in the GPi, recordings from four neurons in the subthalamic nucleus showed almost complete inhibition of firing with clinically effective but not clinically ineffective stimulation parameters. These data provide additional support for the hypothesis of stimulation-evoked GABA release from afferent synaptic terminals and reduction of neuronal firing during DBS and additionally, implicate excitation of GPi axon fibers and neurons and enhancement of inhibitory synaptic transmission by high-frequency GPi DBS as additional putative mechanisms underlying the clinical benefits of DBS in dystonia.

Modulation of synaptic transmission at Ia-afferent fiber connections on motoneurons during high-frequency stimulation: role of postsynaptic target

1991 ◽  
Vol 65 (3) ◽  
pp. 590-597 ◽  
Author(s):  
H. R. Koerber ◽  
L. M. Mendell
Keyword(s):  
High Frequency ◽  
Afferent Fiber ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Epsp Amplitude ◽  
Marked Variability ◽  
Frequency Stimulation ◽  
Frequency Burst ◽  
Stimulation Of

1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory postsynaptic potential (EPSP) amplitude recorded in target motoneurons. This can be either positive (EPSP amplitude increases in response to successive stimuli in the high-frequency burst) or negative (decrease in EPSP amplitude). We have investigated whether the magnitude of modulation is associated with the stimulated afferent, the responding motoneuron, or the amplitude of the EPSP. 2. In agreement with previous findings, we found that positive modulation tends to occur at connections generating small EPSPs and negative modulation, at those producing large EPSPs. Because large EPSPs generally are evoked in motoneurons with low values of rheobase, we found, as anticipated, that connections on low rheobase motoneurons are prone to negative modulation during high-frequency stimulation, whereas those on high rheobase motoneurons (which tend to generate small EPSPs) are prone to positive modulation. 3. In experiments where the projection of multiple afferents to a single motoneuron was studied, we found that amplitude modulation was similar despite differences in EPSP amplitude. Thus in a given motoneuron there is no relationship between modulation and amplitude, in contrast to the existence of such a relationship in the population of connections as a whole. 4. In the converse experiments where the projection of single afferents to multiple motoneurons was studied, we found marked variability in the modulation patterns with clear indications that amplitude and modulation are correlated as in the entire population of Ia/motoneuron connections. 5. We tested the constancy of modulation patterns evoked in a given motoneuron by comparing the modulation patterns evoked in motoneurons by single fibers, and by stimulation of the heteronymous nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jian Qiu ◽  
Casey C Nestor ◽  
Chunguang Zhang ◽  
Stephanie L Padilla ◽  
Richard D Palmiter ◽  
...  
Keyword(s):  
High Frequency ◽  
Pubertal Development ◽  
Reproductive Function ◽  
Neuronal Firing ◽  
High Frequency Stimulation ◽  
Peptide Release ◽  
Gnrh Neurons ◽  
Hypothalamic Arcuate Nucleus ◽  
Frequency Stimulation ◽  
Local Release

Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function.

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