scholarly journals Slack, Slick, and Sodium-Activated Potassium Channels

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Leonard K. Kaczmarek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Potassium Channels ◽  
Ampa Receptors ◽  
Neuronal Plasticity ◽  
Action Potentials ◽  
Neurotransmitter Receptors ◽  
Learning And Development ◽  
Intellectual Function ◽  
The Central Nervous System

The Slack and Slick genes encode potassium channels that are very widely expressed in the central nervous system. These channels are activated by elevations in intracellular sodium, such as those that occur during trains of one or more action potentials, or following activation of nonselective cationic neurotransmitter receptors such as AMPA receptors. This review covers the cellular and molecular properties of Slack and Slick channels and compares them with findings on the properties of sodium-activated potassium currents (termed KNa currents) in native neurons. Human mutations in Slack channels produce extremely severe defects in learning and development, suggesting that KNa channels play a central role in neuronal plasticity and intellectual function.

Comparison of the Effects of Convulsant and Depressant Barbiturate Stereoisomers on AMPA-type Glutamate Receptors

1999 ◽  
Vol 90 (6) ◽  
pp. 1704-1713. ◽  
Author(s):  
Yoshinori Kamiya ◽  
Tomio Andoh ◽  
Ryosuke Furuya ◽  
Satoshi Hattori ◽  
Itaru Watanabe ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Dependent Manner ◽  
Induced Current ◽  
Gaba A ◽  
The Central Nervous System

Background Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system. Although barbiturates have been shown to suppress the AMPA receptor-mediated responses, it is unclear whether this effect contributes to the anesthetic action of barbiturates. The authors compared the effects of depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) on the AMPA and gamma-aminobutyric acid type A (GABA(A)) receptor-mediated currents to determine if the inhibitory effects on AMPA receptors correlate to the in vivo effects of the isomers. Method The authors measured whole-cell currents in the rat cultured cortical neuron at holding potential of -60 mV. Kainate 500 microM was applied as the agonist for AMPA receptors. Thiopental (3-300 microM), R(-)-MPPB or S(+)-MPPB (100-1,000 microM) was coapplied with kainate under the condition in which the GABA(A) receptor-mediated current was blocked. Effects of MPPB isomers on the current elicited by GABA 1 microM were studied in the separate experiments. Results Thiopental inhibited the kainate-induced current reversibly and in a dose-dependent manner, with a concentration for 50% inhibition of 49.3 microM. Both R(-)-MPPB and S(+)-MPPB inhibited the kainate-induced current with a little stereoselectivity. R(-)-MPPB was slightly but significantly more potent than S(+)-MPPB. In contrast, R(-)-MPPB enhanced but S(+)-MPPB reduced the GABA-induced current. Conclusions Both convulsant and depressant stereoisomers of the barbiturate inhibited the AMPA receptor-mediated current despite of their opposite effects on the central nervous system in vivo. Although thiopental exhibited a considerable inhibition of AMPA receptors, the results suggest that the inhibition of AMPA receptors contributes little to the hypnotic action of the barbiturates.

scholarly journals Reduced motoneuron excitability in a rat model of sepsis

2013 ◽  
Vol 109 (7) ◽  
pp. 1775-1781 ◽  
Author(s):  
Paul Nardelli ◽  
Jaffar Khan ◽  
Randall Powers ◽  
Tim C. Cope ◽  
Mark M. Rich
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Intensive Care ◽  
Motor Unit ◽  
Action Potentials ◽  
Cecal Ligation ◽  
Membrane Properties ◽  
Whole Body ◽  
Repetitive Firing ◽  
The Central Nervous System

Many critically ill patients in intensive care units suffer from an infection-induced whole body inflammatory state known as sepsis, which causes severe weakness in patients who survive. The mechanisms by which sepsis triggers intensive care unit-acquired weakness (ICUAW) remain unclear. Currently, research into ICUAW is focused on dysfunction of the peripheral nervous system. During electromyographic studies of patients with ICUAW, we noticed that recruitment was limited to few motor units, which fired at low rates. The reduction in motor unit rate modulation suggested that functional impairment within the central nervous system contributes to ICUAW. To understand better the mechanism underlying reduced firing motor unit firing rates, we moved to the rat cecal ligation and puncture model of sepsis. In isoflurane-anesthetized rats, we studied the response of spinal motoneurons to injected current to determine their capacity for initiating and firing action potentials repetitively. Properties of single action potentials and passive membrane properties of motoneurons from septic rats were normal, suggesting excitability was normal. However, motoneurons exhibited striking dysfunction during repetitive firing. The sustained firing that underlies normal motor unit activity and smooth force generation was slower, more erratic, and often intermittent in septic rats. Our data are the first to suggest that reduced excitability of neurons within the central nervous system may contribute to ICUAW.

Mechanisms Shaping Fast Excitatory Postsynaptic Currents in the Central Nervous System

2002 ◽  
Vol 14 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Mladen I. Glavinović
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ampa Receptors ◽  
Time Course ◽  
Basic Element ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Theoretical Investigations ◽  
The Central Nervous System ◽  
New Hypothesis

How different factors contribute to determine the time course of the basic element of fast glutamate-mediated excitatory postsynaptic currents (mEPSCs) in the central nervous system has been a focus of interest of neurobiologists for some years. In spite of intensive investigations, these mechanisms are not well understood. In this review, basic hypotheses are summarized, and a new hypothesis is proposed, which holds that desensitization of AMPA receptros plays a major role in shaping the time course of fast mEPSCs. According to the new hypothesis, desensitization shortens the time course of mEPSCs largely by reducing the buffering of glutamate molecules by AMPA receptors. The hypothesis accounts for numerous findings on fast mEPSCs and is expected to be equally fruitful as a framework for further experimental and theoretical investigations.

An electrophysiological analysis of extra-axonal sodium and potassium concentrations in the central nervous system of the cockroach (Periplaneta americana L.)

1975 ◽  
Vol 63 (3) ◽  
pp. 801-811
Author(s):  
M. V. Thomas ◽  
J. E. Treherne
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Action Potentials ◽  
Periplaneta Americana ◽  
Sodium Concentration ◽  
Blood Potassium ◽  
The Central Nervous System ◽  
Sucrose Gap ◽  
Sodium And Potassium

Simultaneous intracellular and sucrose-gap recordings showed, in contrast to previous findings, that the electrical parameters of giant axons were similar to intact and desheathed connectives bathed with the ‘extracellular Ringer’ of Yamasaki & Narahashi. This implies that the extra-axonal sodium concentration, in situ, is likely to be lower than had been previously supposed. Axonal responses showed that, despite the high blood concentration of 24–2 mM-K+ measured by flame photometry, the effective concentration in the blood was 10–15 mM-K+ which corresponds to the measurements made with potassium-selective electrodes. The activity of the blood potassium ions caused a marked reduction in the amplitude of the action potentials following surgical desheathing or disruption of the blood-brain barrier with hypertonic urea. It is suggested that a regulatory mechanism exists in the central nervous system which counteracts the effects of the high blood potassium level.

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