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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Veröffentlicht in:Investigative ophthalmology & visual science 2005-01, Vol.46 (1), p.390-397
Hauptverfasser: Kawai, Fusao, Horiguchi, Masayuki, Ichinose, Hiroshi, Ohkuma, Mahito, Isobe, Ryoko, Miyachi, Ei-ichi
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container_title Investigative ophthalmology & visual science
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creator Kawai, Fusao
Horiguchi, Masayuki
Ichinose, Hiroshi
Ohkuma, Mahito
Isobe, Ryoko
Miyachi, Ei-ichi
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.
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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. 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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. 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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 &amp; 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 &amp; 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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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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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