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Fujio Murakami

Publications and source records attributed to Fujio Murakami.

28 records · Page 2Linked to original sources
PubMed2003

Rundown of a transient potassium current is attributable to changes in channel voltage dependence.

Many ionic currents undergo significant rundown during whole-cell recording. Although rundown is an artifact associated with the recording method, studying the mechanism of rundown may lead to understanding mechanisms regulating channel functions in physiological conditions. The mechanisms for rundown, however, remain obscure for many channels. Here we have studied the mechanism for rundown of an A-type K(+) current in mouse striatal cholinergic interneurons. The interneuron expressed a prominent component of A-type current which exhibited significant rundown during whole-cell recording. When the current was assessed with a highly hyperpolarized prepotential (-140 mV), however, the rundown was virtually fully suppressed, suggesting its being dependent on voltage. Estimation of channel voltage dependence revealed that both activation and inactivation curves shifted towards hyperpolarized potentials during rundown. The shift was suppressed by intracellular ATP, but was affected neither by phosphatase inhibitors nor by antioxidative reagents. The gradual shift of inactivation curve towards negative potentials would make the holding potential progressively inactivate the channel, resulting in apparent loss of activity of the channels. Our results thus provide a biophysical explanation for rundown of A-type current. .

Action Potentials↗
PubMed2003

MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents.

Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo-cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1-related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labelling and anti-MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell-adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth-promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.

Aging↗
PubMed2003

Quantitative relationship between Kv4.2 mRNA and A-type K+ current in rat striatal cholinergic interneurons during development.

Channel density is a fundamental factor in determining neuronal firing and is primarily regulated during development through transcriptional and translational regulation. In adult rats, striatal cholinergic interneurons have a prominent A-type current and co-express Kv4.1 and Kv4.2 mRNAs. There is evidence that Kv4.2 plays a primary role in producing the current in adult neurons. The contribution of Kv4.2 and Kv4.1 to the A-type current in cholinergic interneurons during development, however, is not known. Here, using patch-clamp recording and semi-quantitative single-cell reverse transcription-polymerase chain reaction (RT-PCR) techniques, we have examined the postnatal development of A-type current and the expression of Kv4.2 and Kv4.1 in rat striatal cholinergic interneurons. A-type current was detectable at birth, and its amplitude was up-regulated with age, reaching a plateau at about 3 wk after birth. At all ages, the current inactivated with two time constants: one ranging from 15 to 27 ms and the other ranging from 99 to 142 ms. Kv4.2 mRNA was detectable at birth, and the expression level increased exponentially with age, reaching a plateau by 3 wk postnatal. In contrast, Kv4.1 mRNA was not detectable during the first week after birth, and the expression level did not show a clear tendency with age. Taken together, our results suggest that Kv4.2 plays an essential role in producing the A-type current in striatal cholinergic interneurons during the entire course of postnatal development.

Acetylcholine↗
PubMed2002

In vitro analysis of the origin, migratory behavior, and maturation of cortical pyramidal cells.

During development neurons migrate from their site of origin to their final destinations under a variety of mechanisms. Although evidence has been accumulating that the cells from cortical ventricular zone (VZ) migrate radially and produce pyramidal cells, evidence that directly links the origin and the terminal phenotype of radially migrating cells has been limited. Further, the relation between the migratory behavior of these cells and their mature morphology remains obscure. To address these issues, we developed an in vitro preparation that enables visualization of cells derived from the cortical VZ. VZ cells of a rat cortex at embryonic days 18 to 19 were labeled by injecting green fluorescent protein (GFP)-encoding plasmid into the lateral ventricle, followed by electroporation. The cortex was then sliced and cultured organotypically. After 1 day, GFP(+) cells exhibited neural progenitor and radial glial cell natures. Over the next few days, many GFP(+) cells migrated toward the pial surface, extending leading processes toward the pial surface and leaving a thin trailing process that almost reached the VZ. The leading processes of these neurons were positive for microtubule-associated protein 2, and some transformed into dendritic arbor-like structures by day 5 or 6, and their trailing processes exhibited morphologic features indicative of prospective axons. Time-lapse analysis confirmed extension of the trailing processes. Expression of molecular markers and morphologic analysis demonstrated that the vast majority of the migrated GFP(+) cells differentiated into excitatory neurons with pyramidal cell-like morphology. These results strongly suggested that cells derived from the cortical VZ generate neurons that migrate radially. These neurons appeared to extend prospective dendrites in front and leave prospective axons behind, subsequently differentiating into pyramidal cells.

Animals↗
PubMed2002

Crossing the ventral midline causes neurons to change their response to floor plate and alar plate attractive cues during transmedian migration.

Neuronal migration is required for the establishment of specific neural structures, such as layers and nuclei. Neurons migrate along specific migratory routes toward their final destinations, sometimes across long distances. However, the cellular and molecular interactions that control neuronal migration are largely unknown. Here, we examined the mechanism underlying the transmedian migration of precerebellar neurons using a flat whole-mount preparation of the rat embryo. These neurons were initially attracted by the floor plate (FP) at the ventral midline. However, after crossing the midline, they lost their responsiveness to the FP and became attracted by the alar plate (AP). Although the loss of responsiveness to FP cues was caused by an encounter of migrating cells with the FP, the gain of responsiveness to AP cues occurred irrespective of their encounter with the FP. These results identify a crucial change in the response of migrating cells to attractive guidance cues during the transmedian migration of precerebellar neurons.

Animals↗
PubMed2002

Wiring of the brain by a range of guidance cues.

During development of the central nervous system, growth cones navigate along specific pathways, recognize their targets and then form synaptic connections by elaborating terminal arbors. To date, a number of developmental and in vitro studies have characterized the nature of the guidance cues that underlie various types of axonal behavior, from initial outgrowth to synapse formation, including pathway selection, polarized growth, orientated growth, termination and branching. New approaches in molecular biology have identified several types of guidance cues, most of which are likely to act as local cues. Moreover, recent studies have indicated that axonal responsiveness to guidance cues changes dynamically, which appears to be elicited by environmental factors encountered by the navigating growth cones. This article addresses what molecular cues are responsible for guidance mechanisms including axonal responsiveness, focusing on axonal behavior in the developmental stages.

Axons↗
PubMed2002

Effects of secretin on TCDCA- or TDCA-induced cholestatic liver injury in the rat.

Secretin, a gastrointestinal hormone, is known to act on bile duct epithelial cells and has been thought to have no effects on the bile acid transport in the liver. However, secretin was proved recently to stimulate biliary secretion of taurocholic acid (TCA) and elevate the maximum hepatic transport capacity of TCA. In this study, to evaluate the effect of secretin on the biliary secretion of taurochenodeoxycholic acid (TCDCA) or taurodeoxycholic acid (TDCA), which are known as cytotoxic bile acids, changes in bile flow, biliary excretions of bile acids and serum levels of TCDCA or TDCA were studied in a TCDCA- or TDCA-induced cholestatic rat model with and without secretin administration. Secretin prevented the decrease in bile flow and enhanced biliary excretions of bile acids and bicarbonate, but serum levels of TCDCA or TDCA at the end of the study showed no significant changes in the secretin group as compared with controls. Serum levels of alanine and asparate aminotransferases were highly elevated in all rats given TCDCA or TDCA. These data indicate secretin is a possible treatment for patients with prolonged intrahepatic cholestasis.

Journal Article↗
PubMed2002

Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone.

Precisely regulated radial migration out of the ventricular zone is essential for corticogenesis. Here, we identify a mechanism that can tether ventricular zone cells in situ. FILIP interacts with Filamin A, an indispensable actin-binding protein that is required for cell motility, and induces its degradation in COS-7 cells. Degradation of Filamin A is identified in the cortical ventricular zone, where filip mRNA is localized. Furthermore, most ventricular zone cells that overexpress FILIP fail to migrate in explants. These results demonstrate that FILIP functions through a Filamin A F-actin axis to control the start of neocortical cell migration from the ventricular zone.

Actins↗
PubMed2002

Ephrin-B3-EphA4 interactions regulate the growth of specific thalamocortical axon populations in vitro.

The role was studied of ephrin-B3, a ligand of the Eph family of tyrosine kinase receptors, in the formation of cortical connectivity. In situ hybridization and immunohistochemistry showed that EphA4, a receptor of ephrin-B3, was expressed in the lateral thalamus (visual and somaotosensory thalamus) of the developing rat brain, but not in the medial thalamic nuclei which project to the limbic cortex. Correspondingly, ephrin-B3 was expressed strongly in the developing limbic cortex including amygdala, entorhinal cortex and hippocampus. To examine the action of ephrin-B3 on thalamic axons, either lateral or medial thalamic explants were cultured on membranes obtained from ephrin-B3-expressing COS cells. Axonal growth was inhibited for cells from the lateral thalamus but not from the medial thalamus. These results suggest that ephrin-B3 contributes to regional specificity by suppressing axonal growth of lateral thalamic neurons.

Animals↗