大脳皮質錐体細胞の発火様式とその働き

The regular spiking pattern has been demonstrated to change into a fast rhythmic bursting pattern in some pyramidal cells (Kang & Kayano, 1994). The fast rhythmic bursting pattern is presumed to play a crucial role in evoking the gamma-band EEG oscillation that emerges on cognition or on rehearsal of short-term memory (Gray & McCormick, 1996). Since the enhancement of depolarizing afterpotentials (DAP) appeared to be involved in the transformation of firing patterns, we investigated the ionic mechanisms underlying the DAP and its potentiation in pyramidal cells in rat frontal cortical slices using the whole-cell recording method. The generation of DAP was found to be mediated by a Ca^ dependent cationic current (Kang, Okada & Ohmori, 1998). Furthermore, the Ca^ dependent cationic current was found to be enhanced Ca^-dependently. This would be consistent with our previous observation that repetitive application of strong depolarization induced fast rhythmic burst firing as a consequence of an enhancement of DAP, because the intracellular Ca^ concentration increases following repetitive strong membrane depolarization

The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus.

Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K(+) channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15-20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN

Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABAA Receptors with a Special Reference to Propofol/Barbiturate

It is known that desensitization of GABAA receptor (GABAAR)-mediated currents is paradoxically correlated with the slowdown of their deactivation, i.e., resensitization. It has been shown that an upregulation of calcineurin enhances the desensitization of GABAAR-mediated currents but paradoxically prolongs the decay phase of inhibitory postsynaptic currents/potentials without appreciable diminution of their amplitudes. The paradoxical correlation between desensitization and resensitization of GABAAR-mediated currents can be more clearly seen in response to a prolonged application of GABA to allow more desensitization, instead of brief pulse used in previous studies. Indeed, hump-like GABAAR currents were produced after a strong desensitization at the offset of a prolonged puff application of GABA in pyramidal cells of the barrel cortex, in which calcineurin activity was enhanced by deleting phospholipase C-related catalytically inactive proteins to enhance the desensitization/resensitization of GABAAR-mediated currents. Hump-like GABAAR currents were also evoked at the offset of propofol or barbiturate applications in hippocampal or sensory neurons, but not GABA applications. Propofol and barbiturate are useful to treat benzodiazepine/alcohol withdrawal syndrome, suggesting that regulatory mechanisms of desensitization/resensitization of GABAAR-mediated currents are important in understanding benzodiazepine/alcohol withdrawal syndrome. In this review, we will discuss the molecular and regulatory mechanisms underlying the desensitization and resensitization of GABAAR-mediated currents and their functional significances

Gas Metal Arc Welding Using Novel CaO-Added Mg Alloy Filler Wire

Novel “ECO Mg” alloys, i.e., CaO-added Mg alloys, which exhibit oxidation resistance during melting and casting processes, even without the use of beryllium or toxic protection gases such as SF6, have recently been introduced. Research on ECO Mg alloys is still continuing, and their application as welding filler metals was investigated in this study. Mechanical and metallurgical aspects of the weldments were analysed after welding, and welding behaviours such as fume generation and droplet transfer were observed during welding. The tensile strength of welds was slightly increased by adding CaO to the filler metal, which resulted from the decreased grain size in the weld metal. When welding Mg alloys, fumes have been unavoidable so far because of the low boiling temperature of Mg. Fume reduction was successfully demonstrated with a wire composed of the novel ECO Mg filler. In addition, stable droplet transfer was observed and spatter suppression could be expected by using CaO-added Mg filler wire

Subcellular Localization of Homomeric TASK3 Channels and Its Presumed Functional Significances in Trigeminal Motoneurons

Somatic expressions of either heteromeric TASK1/3 or homomeric TASK1/1 channels have been reported in various neurons, while expression of homomeric TASK3/3 channels has been re-ported only in dendrites. However, it is not known why homomeric TASK3/3 channels are hardly seen in somata of CNS neurons. Given the absence of somatic TASK3/3 channels, it should be clarified why dendritic expression of TASK3/3 channels is inevitable and necessary and how differentially distributed TASK1/1 and TASK3/3 channels play roles in soma-to-dendritic integration. Here, we addressed these questions. We found that TASK3-transfected HEK293 cells showed decreases in cell volume after being transferred from the cultured medium to HEPES Ringer, suggesting that expressions of TASK3 channels in cell bodies cause an osmolarity problem. Using TASK1- and TASK3-transfected oocytes, we also found that cGMP application slightly suppressed TASK3 currents while it largely enhanced TASK1 currents, alleviating the difference between TASK1 and TASK3 currents at physiological pH. As larger motoneurons have extensive dendritic trees while smaller motoneurons have poor ones, cGMP could integrate Ia-EPSPs to recruit small and large motoneurons synchronously by differentially modulating TASKI and TASK3 channels which were complementary distributed in soma and dendrites of motoneurons in the dorsolateral part of the trigeminal motor nucleus