Suppression by an h Current of Spontaneous Na+ Action Potentials in Human Cone and Rod Photoreceptors
The sense of vision in humans is robust, and visual flickering is rarely experienced. To investigate this mechanism, electrophysiological and molecular biological techniques were used on human cone and rod photoreceptors. Voltage-gated currents were recorded using the patch-clamp technique on isolat...
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description | The sense of vision in humans is robust, and visual flickering is rarely experienced. To investigate this mechanism, electrophysiological and molecular biological techniques were used on human cone and rod photoreceptors.
Voltage-gated currents were recorded using the patch-clamp technique on isolated human cones, and especially their voltage-gated Na+ currents were analyzed in detail. Whether Na+ channel transcripts could be detected in single photoreceptors using RT-PCR was also examined, to test the expression of voltage-gated Na+ channels in cones and/or rods.
Under current-clamp conditions, blocking h currents (hyperpolarization-activated cationic currents) with Cs+, Tl+, or ZD7288 hyperpolarized the resting potentials of cones and rods by approximately 10 to 15 mV, and surprisingly generated spontaneous action potentials. The spontaneous spikes were blocked by 1 microM tetrodotoxin, but not by 1 mM Co2+, suggesting that they were Na+ spikes rather than Ca2+ spikes. Under voltage-clamp conditions, application of Cs+ and ZD7288 markedly decreased the steady inward current through the h channel. This is consistent with Cs+-induced hyperpolarization under a current-clamp condition. SCN2 Na+ channel was observed in both cones and rods by single-cell RT-PCR analysis, suggesting that human photoreceptors express the SCN2 Na+ channel.
The data confirmed that voltage-gated Na+ channels were expressed not only in human rods but also in cones by electrophysiological and molecular biological experiments. These results suggest that the h current may contribute to preventing visual flickering by inhibiting the generation of spontaneous Na+ spikes in human photoreceptors. |
doi_str_mv | 10.1167/iovs.04-0724 |
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Voltage-gated currents were recorded using the patch-clamp technique on isolated human cones, and especially their voltage-gated Na+ currents were analyzed in detail. Whether Na+ channel transcripts could be detected in single photoreceptors using RT-PCR was also examined, to test the expression of voltage-gated Na+ channels in cones and/or rods.
Under current-clamp conditions, blocking h currents (hyperpolarization-activated cationic currents) with Cs+, Tl+, or ZD7288 hyperpolarized the resting potentials of cones and rods by approximately 10 to 15 mV, and surprisingly generated spontaneous action potentials. The spontaneous spikes were blocked by 1 microM tetrodotoxin, but not by 1 mM Co2+, suggesting that they were Na+ spikes rather than Ca2+ spikes. Under voltage-clamp conditions, application of Cs+ and ZD7288 markedly decreased the steady inward current through the h channel. This is consistent with Cs+-induced hyperpolarization under a current-clamp condition. SCN2 Na+ channel was observed in both cones and rods by single-cell RT-PCR analysis, suggesting that human photoreceptors express the SCN2 Na+ channel.
The data confirmed that voltage-gated Na+ channels were expressed not only in human rods but also in cones by electrophysiological and molecular biological experiments. These results suggest that the h current may contribute to preventing visual flickering by inhibiting the generation of spontaneous Na+ spikes in human photoreceptors.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.04-0724</identifier><identifier>PMID: 15623800</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Action Potentials - physiology ; Adult ; Aged ; Biological and medical sciences ; Cesium - pharmacology ; Cyclic Nucleotide-Gated Cation Channels ; Eye and associated structures. Visual pathways and centers. Vision ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Ion Channels - genetics ; Ion Channels - metabolism ; Middle Aged ; Patch-Clamp Techniques ; Potassium Channels ; Pyrimidines - pharmacology ; Retinal Cone Photoreceptor Cells - drug effects ; Retinal Cone Photoreceptor Cells - physiology ; Retinal Rod Photoreceptor Cells - drug effects ; Retinal Rod Photoreceptor Cells - physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Sodium - metabolism ; Sodium Channels - genetics ; Sodium Channels - metabolism ; Tetrodotoxin - pharmacology ; Vertebrates: nervous system and sense organs</subject><ispartof>Investigative ophthalmology & visual science, 2005-01, Vol.46 (1), p.390-397</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-d9bec5080b3646a0f7314f0411de22fd9f2f74a70724b577971f7830585e2bb43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16439489$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15623800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawai, Fusao</creatorcontrib><creatorcontrib>Horiguchi, Masayuki</creatorcontrib><creatorcontrib>Ichinose, Hiroshi</creatorcontrib><creatorcontrib>Ohkuma, Mahito</creatorcontrib><creatorcontrib>Isobe, Ryoko</creatorcontrib><creatorcontrib>Miyachi, Ei-ichi</creatorcontrib><title>Suppression by an h Current of Spontaneous Na+ Action Potentials in Human Cone and Rod Photoreceptors</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>The sense of vision in humans is robust, and visual flickering is rarely experienced. To investigate this mechanism, electrophysiological and molecular biological techniques were used on human cone and rod photoreceptors.
Voltage-gated currents were recorded using the patch-clamp technique on isolated human cones, and especially their voltage-gated Na+ currents were analyzed in detail. Whether Na+ channel transcripts could be detected in single photoreceptors using RT-PCR was also examined, to test the expression of voltage-gated Na+ channels in cones and/or rods.
Under current-clamp conditions, blocking h currents (hyperpolarization-activated cationic currents) with Cs+, Tl+, or ZD7288 hyperpolarized the resting potentials of cones and rods by approximately 10 to 15 mV, and surprisingly generated spontaneous action potentials. The spontaneous spikes were blocked by 1 microM tetrodotoxin, but not by 1 mM Co2+, suggesting that they were Na+ spikes rather than Ca2+ spikes. Under voltage-clamp conditions, application of Cs+ and ZD7288 markedly decreased the steady inward current through the h channel. This is consistent with Cs+-induced hyperpolarization under a current-clamp condition. SCN2 Na+ channel was observed in both cones and rods by single-cell RT-PCR analysis, suggesting that human photoreceptors express the SCN2 Na+ channel.
The data confirmed that voltage-gated Na+ channels were expressed not only in human rods but also in cones by electrophysiological and molecular biological experiments. These results suggest that the h current may contribute to preventing visual flickering by inhibiting the generation of spontaneous Na+ spikes in human photoreceptors.</description><subject>Action Potentials - physiology</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Cesium - pharmacology</subject><subject>Cyclic Nucleotide-Gated Cation Channels</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels</subject><subject>Ion Channels - genetics</subject><subject>Ion Channels - metabolism</subject><subject>Middle Aged</subject><subject>Patch-Clamp Techniques</subject><subject>Potassium Channels</subject><subject>Pyrimidines - pharmacology</subject><subject>Retinal Cone Photoreceptor Cells - drug effects</subject><subject>Retinal Cone Photoreceptor Cells - physiology</subject><subject>Retinal Rod Photoreceptor Cells - drug effects</subject><subject>Retinal Rod Photoreceptor Cells - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sodium - metabolism</subject><subject>Sodium Channels - genetics</subject><subject>Sodium Channels - metabolism</subject><subject>Tetrodotoxin - pharmacology</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0M1LwzAYBvAgipvTm2fJxZN2vvlo0x5HUScMHU7PIW0TV9makrSO_fembLDTe_m9DzwPQrcEpoQk4qm2f34KPAJB-RkakzimUSxSdo7GQHgSAQc-Qlfe_wJQQihcohGJE8pSgDHSq75tnfa-tg0u9lg1eI3z3jnddNgavGpt06lG297jd_WAZ2U3yKXtAqjVxuO6wfN-G_5y2-jwX-FPW-Hl2nbW6VK34fhrdGGC1TfHO0HfL89f-TxafLy-5bNFVLKMdVGVFbqMIYWCJTxRYAQj3AAnpNKUmioz1AiuxFC1iIXIBDGhKcRprGlRcDZBj4fc0lnvnTaydfVWub0kIIe15LCWBC6HiMDvDrzti62uTvg4TwD3R6B8qTbGqaas_cklnGU8zU5uXf-sd7XT0m_VZhNiidztdjyRRLIM2D94rn-I</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>Kawai, Fusao</creator><creator>Horiguchi, Masayuki</creator><creator>Ichinose, Hiroshi</creator><creator>Ohkuma, Mahito</creator><creator>Isobe, Ryoko</creator><creator>Miyachi, Ei-ichi</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20050101</creationdate><title>Suppression by an h Current of Spontaneous Na+ Action Potentials in Human Cone and Rod Photoreceptors</title><author>Kawai, Fusao ; Horiguchi, Masayuki ; Ichinose, Hiroshi ; Ohkuma, Mahito ; Isobe, Ryoko ; Miyachi, Ei-ichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-d9bec5080b3646a0f7314f0411de22fd9f2f74a70724b577971f7830585e2bb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Action Potentials - physiology</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Cesium - pharmacology</topic><topic>Cyclic Nucleotide-Gated Cation Channels</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels</topic><topic>Ion Channels - genetics</topic><topic>Ion Channels - metabolism</topic><topic>Middle Aged</topic><topic>Patch-Clamp Techniques</topic><topic>Potassium Channels</topic><topic>Pyrimidines - pharmacology</topic><topic>Retinal Cone Photoreceptor Cells - drug effects</topic><topic>Retinal Cone Photoreceptor Cells - physiology</topic><topic>Retinal Rod Photoreceptor Cells - drug effects</topic><topic>Retinal Rod Photoreceptor Cells - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Sodium - metabolism</topic><topic>Sodium Channels - genetics</topic><topic>Sodium Channels - metabolism</topic><topic>Tetrodotoxin - pharmacology</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawai, Fusao</creatorcontrib><creatorcontrib>Horiguchi, Masayuki</creatorcontrib><creatorcontrib>Ichinose, Hiroshi</creatorcontrib><creatorcontrib>Ohkuma, Mahito</creatorcontrib><creatorcontrib>Isobe, Ryoko</creatorcontrib><creatorcontrib>Miyachi, Ei-ichi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawai, Fusao</au><au>Horiguchi, Masayuki</au><au>Ichinose, Hiroshi</au><au>Ohkuma, Mahito</au><au>Isobe, Ryoko</au><au>Miyachi, Ei-ichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression by an h Current of Spontaneous Na+ Action Potentials in Human Cone and Rod Photoreceptors</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2005-01-01</date><risdate>2005</risdate><volume>46</volume><issue>1</issue><spage>390</spage><epage>397</epage><pages>390-397</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>The sense of vision in humans is robust, and visual flickering is rarely experienced. To investigate this mechanism, electrophysiological and molecular biological techniques were used on human cone and rod photoreceptors.
Voltage-gated currents were recorded using the patch-clamp technique on isolated human cones, and especially their voltage-gated Na+ currents were analyzed in detail. Whether Na+ channel transcripts could be detected in single photoreceptors using RT-PCR was also examined, to test the expression of voltage-gated Na+ channels in cones and/or rods.
Under current-clamp conditions, blocking h currents (hyperpolarization-activated cationic currents) with Cs+, Tl+, or ZD7288 hyperpolarized the resting potentials of cones and rods by approximately 10 to 15 mV, and surprisingly generated spontaneous action potentials. The spontaneous spikes were blocked by 1 microM tetrodotoxin, but not by 1 mM Co2+, suggesting that they were Na+ spikes rather than Ca2+ spikes. Under voltage-clamp conditions, application of Cs+ and ZD7288 markedly decreased the steady inward current through the h channel. This is consistent with Cs+-induced hyperpolarization under a current-clamp condition. SCN2 Na+ channel was observed in both cones and rods by single-cell RT-PCR analysis, suggesting that human photoreceptors express the SCN2 Na+ channel.
The data confirmed that voltage-gated Na+ channels were expressed not only in human rods but also in cones by electrophysiological and molecular biological experiments. These results suggest that the h current may contribute to preventing visual flickering by inhibiting the generation of spontaneous Na+ spikes in human photoreceptors.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>15623800</pmid><doi>10.1167/iovs.04-0724</doi><tpages>8</tpages></addata></record> |
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subjects | Action Potentials - physiology Adult Aged Biological and medical sciences Cesium - pharmacology Cyclic Nucleotide-Gated Cation Channels Eye and associated structures. Visual pathways and centers. Vision Fundamental and applied biological sciences. Psychology Gene Expression Humans Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Ion Channels - genetics Ion Channels - metabolism Middle Aged Patch-Clamp Techniques Potassium Channels Pyrimidines - pharmacology Retinal Cone Photoreceptor Cells - drug effects Retinal Cone Photoreceptor Cells - physiology Retinal Rod Photoreceptor Cells - drug effects Retinal Rod Photoreceptor Cells - physiology Reverse Transcriptase Polymerase Chain Reaction Sodium - metabolism Sodium Channels - genetics Sodium Channels - metabolism Tetrodotoxin - pharmacology Vertebrates: nervous system and sense organs |
title | Suppression by an h Current of Spontaneous Na+ Action Potentials in Human Cone and Rod Photoreceptors |
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