Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells
Intracellular Ca(2+) ([Ca(2+)](i)) oscillations seen in interstitial cells of Cajal (ICCs) are considered to be the primary pacemaker activity in the gut. Here, we show evidence that periodic Ca(2+) release from intracellular Ca(2+) stores produces [Ca(2+)](i) oscillations in ICCs, using cell cluste...
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| Veröffentlicht in: | Journal of cell science 2004-06, Vol.117 (Pt 13), p.2813-2825 |
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| creator | Aoyama, Masahiro Yamada, Aki Wang, Jing Ohya, Susumu Furuzono, Shinji Goto, Takayo Hotta, Shingo Ito, Yasushi Matsubara, Tatsuaki Shimokata, Kaoru Chen, S R Wayne Imaizumi, Yuji Nakayama, Shinsuke |
| description | Intracellular Ca(2+) ([Ca(2+)](i)) oscillations seen in interstitial cells of Cajal (ICCs) are considered to be the primary pacemaker activity in the gut. Here, we show evidence that periodic Ca(2+) release from intracellular Ca(2+) stores produces [Ca(2+)](i) oscillations in ICCs, using cell cluster preparations isolated from mouse ileum. The pacemaker [Ca(2+)](i) oscillations in ICCs are preserved in the presence of dihydropyridine Ca(2+) antagonists, which suppress Ca(2+) activity in smooth muscle cells. However, applications of drugs affecting either ryanodine receptors or inositol 1,4,5-trisphosphate receptors terminated [Ca(2+)](i) oscillations at relatively low concentrations. RT-PCR analyses revealed a predominant expression of type 3 RyR (RyR3) in isolated c-Kit-immunopositive cells (ICCs). Furthermore, we demonstrate that pacemaker-like global [Ca(2+)](i) oscillation activity is endowed by introducing RyR3 into HEK293 cells, which originally express only IP(3)Rs. The reconstituted [Ca(2+)](i) oscillations in HEK293 cells possess essentially the same pharmacological characteristics as seen in ICCs. The results support the functional role of RyR3 in ICCs. |
| doi_str_mv | 10.1242/jcs.01136 |
| format | Article |
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Here, we show evidence that periodic Ca(2+) release from intracellular Ca(2+) stores produces [Ca(2+)](i) oscillations in ICCs, using cell cluster preparations isolated from mouse ileum. The pacemaker [Ca(2+)](i) oscillations in ICCs are preserved in the presence of dihydropyridine Ca(2+) antagonists, which suppress Ca(2+) activity in smooth muscle cells. However, applications of drugs affecting either ryanodine receptors or inositol 1,4,5-trisphosphate receptors terminated [Ca(2+)](i) oscillations at relatively low concentrations. RT-PCR analyses revealed a predominant expression of type 3 RyR (RyR3) in isolated c-Kit-immunopositive cells (ICCs). Furthermore, we demonstrate that pacemaker-like global [Ca(2+)](i) oscillation activity is endowed by introducing RyR3 into HEK293 cells, which originally express only IP(3)Rs. The reconstituted [Ca(2+)](i) oscillations in HEK293 cells possess essentially the same pharmacological characteristics as seen in ICCs. 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The results support the functional role of RyR3 in ICCs.</description><subject>Anesthetics, Local - pharmacology</subject><subject>Animals</subject><subject>Biological Clocks - drug effects</subject><subject>Biological Clocks - physiology</subject><subject>Boron Compounds - pharmacology</subject><subject>Caffeine - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cell Line</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Fluorescent Dyes</subject><subject>Fura-2</subject><subject>Humans</subject><subject>Ileum - cytology</subject><subject>Ileum - metabolism</subject><subject>Immunohistochemistry</subject><subject>Kinetics</subject><subject>Macrocyclic Compounds</subject><subject>Mice</subject><subject>Microscopy, Fluorescence</subject><subject>Muscle, Smooth - cytology</subject><subject>Muscle, Smooth - metabolism</subject><subject>Nifedipine - pharmacology</subject><subject>Oxazoles - pharmacology</subject><subject>Proto-Oncogene Proteins c-kit - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Ryanodine - metabolism</subject><subject>Ryanodine - pharmacology</subject><subject>Ryanodine Receptor Calcium Release Channel - genetics</subject><subject>Ryanodine Receptor Calcium Release Channel - metabolism</subject><subject>Tacrolimus - pharmacology</subject><subject>Tetracaine - pharmacology</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1LwzAYhYMobk4v_AOSK0GkM2_Sj-RSynTDgSDqbUmTN9C5fixphf17Ox14dTjwcDg8hFwDmwOP-cPGhDkDEOkJmUKcZZECkZ2SKWMcIpUIMSEXIWwYYxlX2TmZQAKpkkJOyecb7obKY41NT1tH_V43ra0apB4Ndn3rA3Wtp502WOsv9DTX_J5q01ffVb-nVUNXeU51Y-ly8cKVoAa323BJzpzeBrw65ox8PC3e82W0fn1e5Y_ryIgE-kgqySW3LB4rQ2mt08pkRigl07J0NuZWluAsBy5YDJikDEEpwxMmlDEoZuT2b7fz7W7A0Bd1FQ4PdIPtEIoMVJpALEfw7g80vg3Boys6X9Xa7wtgxUFiMUosfiWO7M1xdChrtP_k0Zr4AYnoaz8</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Aoyama, Masahiro</creator><creator>Yamada, Aki</creator><creator>Wang, Jing</creator><creator>Ohya, Susumu</creator><creator>Furuzono, Shinji</creator><creator>Goto, Takayo</creator><creator>Hotta, Shingo</creator><creator>Ito, Yasushi</creator><creator>Matsubara, Tatsuaki</creator><creator>Shimokata, Kaoru</creator><creator>Chen, S R Wayne</creator><creator>Imaizumi, Yuji</creator><creator>Nakayama, Shinsuke</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040601</creationdate><title>Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells</title><author>Aoyama, Masahiro ; Yamada, Aki ; Wang, Jing ; Ohya, Susumu ; Furuzono, Shinji ; Goto, Takayo ; Hotta, Shingo ; Ito, Yasushi ; Matsubara, Tatsuaki ; Shimokata, Kaoru ; Chen, S R Wayne ; Imaizumi, Yuji ; Nakayama, Shinsuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c351t-898282d04c350e8ddfa9c7c39986bbfd42d8b1fd2123041e560e199c25039cce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Anesthetics, Local - pharmacology</topic><topic>Animals</topic><topic>Biological Clocks - drug effects</topic><topic>Biological Clocks - physiology</topic><topic>Boron Compounds - pharmacology</topic><topic>Caffeine - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cell Line</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Fluorescent Dyes</topic><topic>Fura-2</topic><topic>Humans</topic><topic>Ileum - cytology</topic><topic>Ileum - metabolism</topic><topic>Immunohistochemistry</topic><topic>Kinetics</topic><topic>Macrocyclic Compounds</topic><topic>Mice</topic><topic>Microscopy, Fluorescence</topic><topic>Muscle, Smooth - cytology</topic><topic>Muscle, Smooth - metabolism</topic><topic>Nifedipine - pharmacology</topic><topic>Oxazoles - pharmacology</topic><topic>Proto-Oncogene Proteins c-kit - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Ryanodine - metabolism</topic><topic>Ryanodine - pharmacology</topic><topic>Ryanodine Receptor Calcium Release Channel - genetics</topic><topic>Ryanodine Receptor Calcium Release Channel - metabolism</topic><topic>Tacrolimus - pharmacology</topic><topic>Tetracaine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aoyama, Masahiro</creatorcontrib><creatorcontrib>Yamada, Aki</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Ohya, Susumu</creatorcontrib><creatorcontrib>Furuzono, Shinji</creatorcontrib><creatorcontrib>Goto, Takayo</creatorcontrib><creatorcontrib>Hotta, Shingo</creatorcontrib><creatorcontrib>Ito, Yasushi</creatorcontrib><creatorcontrib>Matsubara, Tatsuaki</creatorcontrib><creatorcontrib>Shimokata, Kaoru</creatorcontrib><creatorcontrib>Chen, S R Wayne</creatorcontrib><creatorcontrib>Imaizumi, Yuji</creatorcontrib><creatorcontrib>Nakayama, Shinsuke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aoyama, Masahiro</au><au>Yamada, Aki</au><au>Wang, Jing</au><au>Ohya, Susumu</au><au>Furuzono, Shinji</au><au>Goto, Takayo</au><au>Hotta, Shingo</au><au>Ito, Yasushi</au><au>Matsubara, Tatsuaki</au><au>Shimokata, Kaoru</au><au>Chen, S R Wayne</au><au>Imaizumi, Yuji</au><au>Nakayama, Shinsuke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>117</volume><issue>Pt 13</issue><spage>2813</spage><epage>2825</epage><pages>2813-2825</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>Intracellular Ca(2+) ([Ca(2+)](i)) oscillations seen in interstitial cells of Cajal (ICCs) are considered to be the primary pacemaker activity in the gut. Here, we show evidence that periodic Ca(2+) release from intracellular Ca(2+) stores produces [Ca(2+)](i) oscillations in ICCs, using cell cluster preparations isolated from mouse ileum. The pacemaker [Ca(2+)](i) oscillations in ICCs are preserved in the presence of dihydropyridine Ca(2+) antagonists, which suppress Ca(2+) activity in smooth muscle cells. However, applications of drugs affecting either ryanodine receptors or inositol 1,4,5-trisphosphate receptors terminated [Ca(2+)](i) oscillations at relatively low concentrations. RT-PCR analyses revealed a predominant expression of type 3 RyR (RyR3) in isolated c-Kit-immunopositive cells (ICCs). Furthermore, we demonstrate that pacemaker-like global [Ca(2+)](i) oscillation activity is endowed by introducing RyR3 into HEK293 cells, which originally express only IP(3)Rs. The reconstituted [Ca(2+)](i) oscillations in HEK293 cells possess essentially the same pharmacological characteristics as seen in ICCs. The results support the functional role of RyR3 in ICCs.</abstract><cop>England</cop><pmid>15169838</pmid><doi>10.1242/jcs.01136</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anesthetics, Local - pharmacology Animals Biological Clocks - drug effects Biological Clocks - physiology Boron Compounds - pharmacology Caffeine - pharmacology Calcium - metabolism Calcium Channel Blockers - pharmacology Cell Line Enzyme Inhibitors - pharmacology Fluorescent Antibody Technique, Indirect Fluorescent Dyes Fura-2 Humans Ileum - cytology Ileum - metabolism Immunohistochemistry Kinetics Macrocyclic Compounds Mice Microscopy, Fluorescence Muscle, Smooth - cytology Muscle, Smooth - metabolism Nifedipine - pharmacology Oxazoles - pharmacology Proto-Oncogene Proteins c-kit - metabolism RNA, Messenger - metabolism Ryanodine - metabolism Ryanodine - pharmacology Ryanodine Receptor Calcium Release Channel - genetics Ryanodine Receptor Calcium Release Channel - metabolism Tacrolimus - pharmacology Tetracaine - pharmacology |
| title | Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells |
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