Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
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Volume 121, Issue 4
Displaying 1-8 of 8 articles from this issue
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Reviews:Recent Advances in Ca2+ Channel Research
  • Ryanodine receptor and junctional membrane structure
    Hiroshi TAKESHIMA
    Article type: Reviews
    2003 Volume 121 Issue 4 Pages 203-210
    Published: 2003
    Released on J-STAGE: April 11, 2003
    DOIhttps://doi.org/10.1254/fpj.121.203
    JOURNAL FREE ACCESS
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    In excitable cell types, activation of cell-surface Ca2+ channels triggers Ca2+ release from the endplasmic or sarcoplasmic reticulum (ER/SR). This Ca2+ signal amplification, termed Ca2+-induced or voltage-induced Ca2+ release (CICR/VICR), requires the ryanodine receptor as an intracellular Ca2+ channel, which is predominantly localized in the junctional membrane complex between the plasma membrane and the ER/SR. Junctophilin is an ER/SR membrane protein that contributes to the formation of the junctional membrane structure. Ryanodine receptor and junctophilin subtypes are derived from distinct genes and show different tissue-specific expression. Recent gene-knockout studies have defined physiological functions of both Ca2+ release via ryanodine receptors and junctional membrane structures constituted by junctophilins in excitable cells. Moreover, several human genetic diseases are caused by mutations at the ryanodine receptor and junctophilin subtype genes.
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  • N-type Ca2+ channel
    Takashi KURIHARA, Tsutomu TANABE
    Article type: Reviews
    2003 Volume 121 Issue 4 Pages 211-222
    Published: 2003
    Released on J-STAGE: April 11, 2003
    DOIhttps://doi.org/10.1254/fpj.121.211
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    Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) regulates various aspects of physiological function, including neurotransmitter release, regulation of cell membrane excitability, and control of gene expression. VDCCs are classified into several sub-types (L-, N-, P/Q-, R-, and T-types) based on electrophysiological and pharmacological properties. Each type of channels except the T-type is composed of at least four subunits, designated α1, α2, β, and δ. During the past decade, a number of genes encoding these subunits have been cloned, and cDNA expression studies using heterologous expression systems have revealed the intricate nature of subunit interaction and many biophysical aspects of channel function. In recent years, an entirely new strategy has been introduced in attempts to clarify the physiological role of each of the VDCCs, and this has proven to be very useful in defining previously unknown in vivo functions of VDCCs. In this article, we briefly review the recent advances in our understanding of VDCCs with special emphasis on the N-type channel, which is mainly expressed in neural tissues and is the essential component of neurotransmitter release. We will mainly discuss the subunit composition, channel regulation by G proteins and exocytotic proteins, and the mouse phenotypes in which N-type channel subunits have been deleted by gene targeting technology.
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  • TRP channels: formation of signal complex and regulation of cellular functions
    Motohiro NISHIDA, Yuji HARA, Ryuji INOUE, Yasuo MORI
    Article type: Reviews
    2003 Volume 121 Issue 4 Pages 223-232
    Published: 2003
    Released on J-STAGE: April 11, 2003
    DOIhttps://doi.org/10.1254/fpj.121.223
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    Cellular stimulation from the surrounding extracellular environment via receptors and other pathways evoke activation of Ca2+-permeable cation channels. An important clue to understand the molecular mechanisms underlying these receptor-activated cation channels (RACC) was first provided through molecular studies of the transient receptor potential (trp) protein (TRP), which controls light-induced deporlarization in Drosophila photoreceptor cells. Recent studies have revealed that these TRP channels are also activated by diverse stimuli such as heat, osmotic stress, and oxidative stress. Furthermore, involvement of TRP channels has been demonstrated in signaling pathways essential for biological responses, such as proliferation, differentiation, and cell death. These findings encourage usage of TRP channels and their signalplexes as powerful tools for the development of novel pharmaceutical targets.
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  • Alternative splicing of Cav2 genes and their functional significance
    Shuji KANEKO
    Article type: Reviews
    2003 Volume 121 Issue 4 Pages 233-240
    Published: 2003
    Released on J-STAGE: April 11, 2003
    DOIhttps://doi.org/10.1254/fpj.121.233
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    Alternative splicing is one of the most pharmacologically and physiologically significant mechanisms for the functional diversity of the mammalian genomes. Here I review recent results on the diversity of the Cav2 subclass of voltage-dependent Ca2+ channel gene in neurons. Although the entire picture of alternative splicing is not yet understood, emerging evidences suggest the Cav2 isoforms permit optimization of Ca2+ signaling in different regions of the brain with specific pharmacological ligands.
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  • Inositol 1,4,5 trisphosphate (IP3) receptor
    Katsuhiko MIKOSHIBA
    Article type: Reviews
    2003 Volume 121 Issue 4 Pages 241-253
    Published: 2003
    Released on J-STAGE: April 11, 2003
    DOIhttps://doi.org/10.1254/fpj.121.241
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    The intensive molecular and biochemical study of IP3R has made great progress in elucidating the following unique properties of IP3R: 1) IP3 dependent Ca2+ release is quantal in nature; 2) IP3R allosterically and dynamically changes its form; 3) IP3R is functional even though it is fragemented by proteases into several pieces; 4) IP3R forms a functional association with a variety of molecules inside the cell, and with the channels on the plasma membrane; 5) the extremely high IP3 binding affinity (500`1000 times higher than the original IP3R) sequence in the IP3 binding region is covered with a suppressor sequence at the N-terminal. In parallel with these biochemical studies, studies on the role of IP3R during development have greatly advanced. Since IP3R was identified as a developmentally regulated phospho-glycoprotein, the Ca2+ channel P400, it has diverse but essential functions in development and normal cell function.
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Technical Note
  • Analysis of the molecular mechanisms controlling synaptic transmission by patch-clamp recording in brainstem slices
    Fusao KATO, Eiji SHIGETOMI, Masahito KAWAMURA, Ryo IKEDA
    Article type: Technical Note
    2003 Volume 121 Issue 4 Pages 255-263
    Published: 2003
    Released on J-STAGE: April 11, 2003
    DOIhttps://doi.org/10.1254/fpj.121.255
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    The first article describing the patch-clamp recording from neurons in the mammalian brain slice appeared in 1989. Since that article, there have been substantial scientific successes in the neuropharmacological and neurophysiological fields using this promising technique, which itself advanced largely owing to the progress in microscopic techniques such as infrared differential interference contrast (IR-DIC) video-enhanced microscopy. This article describes recent advances in the methods for the patch-clamp recording in the brainstem slices, which is now more and more important due to the increased needs in this post-genomic era for identification of the mechanisms underlying cell-to-cell communication in the central nervous system. Here we introduce some of the technical tips developed and being used in our laboratory, which include methods for making the best brainstem slices, pre-recording identification of neuron types using fluorescent tracers, markers, and green fluorescent protein (GFP) signal in transgenic mice. We also describe a method for rapid and secure drug application onto the recorded cell using electromagnetic valves, which we term the “macro Y-tube” method. These techniques may help to accelerate the understanding of the molecular mechanisms underlying dynamic regulation of central nervous function.
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  • Intermittent microinjection method in freely-moving rats and its application to neuropharmacology
    Satoshi IKEMOTO
    Article type: Technical Note
    2003 Volume 121 Issue 4 Pages 264-267
    Published: 2003
    Released on J-STAGE: April 11, 2003
    DOIhttps://doi.org/10.1254/fpj.121.264
    JOURNAL FREE ACCESS
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    Intermittent delivery of drugs into a discrete brain region has proven to be a useful technique. Described here is a micro-pump injection unit with miniature step-motors. This injection system is reliable, easy to operate and inexpensive to construct. The application of intermittent injection systems to study reward neurochemical circuits is discussed.
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