Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node
The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (I(f)) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 degrees C) and the perforated patch voltage-cla...
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| Veröffentlicht in: | Cardiovascular research 2003-02, Vol.57 (2), p.497-504 |
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| creator | RIGG, Lauren MATTICK, Paul A. D HEATH, Bronagh M TERRAR, Derek A |
| description | The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (I(f)) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 degrees C) and the perforated patch voltage-clamp technique used to record I(f) activated by hyperpolarizing voltage steps. A 10-min loading of SA node cells with the calcium chelator BAPTA (using 10 microM BAPTA-AM) significantly reduced the amplitude of I(f) at all potentials studied (69+/-8% at -80 mV, n=6). BAPTA loading also shifted the voltage of half-activation (V(h)) of the conductance from -83+/-2 mV in control to -93+/-2 mV in BAPTA (n=6) without significantly altering the slope of activation. The calmodulin antagonists W-7 (10 microM), calmidazolium (25 microM) and ophiobolin A (20 microM) caused similar reductions in I(f) amplitude (73+/-4, 86+/-9 and 59+/-6% at -80 mV, n=6, 5 and 4, respectively) and shifts in V(h) (11+/-3, 14+/-3 and 8+/-2 mV). In cells pre-treated with W-7, exposure to BAPTA caused no further reduction in current amplitude (n=6). I(f) current amplitude was unaffected by the calmodulin dependent kinase (CaMKII) inhibitor KN-93 (1 microM) although this CaMKII inhibition did reduce L-type calcium by 48+/-19% at 0 mV (n=3). These results are consistent with a role for calcium and calmodulin in the regulation of I(f), via a mechanism that is independent of CaMKII. Alterations in intracellular calcium during the cardiac cycle may be involved in fine tuning the voltage-dependent properties of I(f) and may thus determine its relative contribution to pacemaking in the SA node. |
| doi_str_mv | 10.1016/s0008-6363(02)00668-5 |
| format | Article |
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D ; HEATH, Bronagh M ; TERRAR, Derek A</creator><creatorcontrib>RIGG, Lauren ; MATTICK, Paul A. D ; HEATH, Bronagh M ; TERRAR, Derek A</creatorcontrib><description>The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (I(f)) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 degrees C) and the perforated patch voltage-clamp technique used to record I(f) activated by hyperpolarizing voltage steps. A 10-min loading of SA node cells with the calcium chelator BAPTA (using 10 microM BAPTA-AM) significantly reduced the amplitude of I(f) at all potentials studied (69+/-8% at -80 mV, n=6). BAPTA loading also shifted the voltage of half-activation (V(h)) of the conductance from -83+/-2 mV in control to -93+/-2 mV in BAPTA (n=6) without significantly altering the slope of activation. The calmodulin antagonists W-7 (10 microM), calmidazolium (25 microM) and ophiobolin A (20 microM) caused similar reductions in I(f) amplitude (73+/-4, 86+/-9 and 59+/-6% at -80 mV, n=6, 5 and 4, respectively) and shifts in V(h) (11+/-3, 14+/-3 and 8+/-2 mV). In cells pre-treated with W-7, exposure to BAPTA caused no further reduction in current amplitude (n=6). I(f) current amplitude was unaffected by the calmodulin dependent kinase (CaMKII) inhibitor KN-93 (1 microM) although this CaMKII inhibition did reduce L-type calcium by 48+/-19% at 0 mV (n=3). These results are consistent with a role for calcium and calmodulin in the regulation of I(f), via a mechanism that is independent of CaMKII. Alterations in intracellular calcium during the cardiac cycle may be involved in fine tuning the voltage-dependent properties of I(f) and may thus determine its relative contribution to pacemaking in the SA node.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1016/s0008-6363(02)00668-5</identifier><identifier>PMID: 12566122</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Benzylamines - pharmacology ; Biological and medical sciences ; Calcium - physiology ; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors ; Calmodulin - antagonists & inhibitors ; Calmodulin - physiology ; Cells, Cultured ; Chelating Agents - pharmacology ; Cyclic Nucleotide-Gated Cation Channels ; Egtazic Acid - analogs & derivatives ; Egtazic Acid - pharmacology ; Enzyme Inhibitors - pharmacology ; Fundamental and applied biological sciences. Psychology ; Guinea Pigs ; Heart ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Ion Channel Gating - drug effects ; Ion Channel Gating - physiology ; Ion Channels - drug effects ; Ion Channels - physiology ; Male ; Membrane Potentials - physiology ; Patch-Clamp Techniques ; Potassium Channels ; Protein Kinase Inhibitors ; Sinoatrial Node - cytology ; Sinoatrial Node - drug effects ; Sinoatrial Node - physiology ; Sulfonamides - pharmacology ; Vertebrates: cardiovascular system</subject><ispartof>Cardiovascular research, 2003-02, Vol.57 (2), p.497-504</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-b825e54972dc17064876723d898e2181fa7064490f2e9116f32dcddef0683c513</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14506776$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12566122$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>RIGG, Lauren</creatorcontrib><creatorcontrib>MATTICK, Paul A. D</creatorcontrib><creatorcontrib>HEATH, Bronagh M</creatorcontrib><creatorcontrib>TERRAR, Derek A</creatorcontrib><title>Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (I(f)) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 degrees C) and the perforated patch voltage-clamp technique used to record I(f) activated by hyperpolarizing voltage steps. A 10-min loading of SA node cells with the calcium chelator BAPTA (using 10 microM BAPTA-AM) significantly reduced the amplitude of I(f) at all potentials studied (69+/-8% at -80 mV, n=6). BAPTA loading also shifted the voltage of half-activation (V(h)) of the conductance from -83+/-2 mV in control to -93+/-2 mV in BAPTA (n=6) without significantly altering the slope of activation. The calmodulin antagonists W-7 (10 microM), calmidazolium (25 microM) and ophiobolin A (20 microM) caused similar reductions in I(f) amplitude (73+/-4, 86+/-9 and 59+/-6% at -80 mV, n=6, 5 and 4, respectively) and shifts in V(h) (11+/-3, 14+/-3 and 8+/-2 mV). In cells pre-treated with W-7, exposure to BAPTA caused no further reduction in current amplitude (n=6). I(f) current amplitude was unaffected by the calmodulin dependent kinase (CaMKII) inhibitor KN-93 (1 microM) although this CaMKII inhibition did reduce L-type calcium by 48+/-19% at 0 mV (n=3). These results are consistent with a role for calcium and calmodulin in the regulation of I(f), via a mechanism that is independent of CaMKII. Alterations in intracellular calcium during the cardiac cycle may be involved in fine tuning the voltage-dependent properties of I(f) and may thus determine its relative contribution to pacemaking in the SA node.</description><subject>Animals</subject><subject>Benzylamines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Calcium - physiology</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors</subject><subject>Calmodulin - antagonists & inhibitors</subject><subject>Calmodulin - physiology</subject><subject>Cells, Cultured</subject><subject>Chelating Agents - pharmacology</subject><subject>Cyclic Nucleotide-Gated Cation Channels</subject><subject>Egtazic Acid - analogs & derivatives</subject><subject>Egtazic Acid - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guinea Pigs</subject><subject>Heart</subject><subject>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels</subject><subject>Ion Channel Gating - drug effects</subject><subject>Ion Channel Gating - physiology</subject><subject>Ion Channels - drug effects</subject><subject>Ion Channels - physiology</subject><subject>Male</subject><subject>Membrane Potentials - physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Potassium Channels</subject><subject>Protein Kinase Inhibitors</subject><subject>Sinoatrial Node - cytology</subject><subject>Sinoatrial Node - drug effects</subject><subject>Sinoatrial Node - physiology</subject><subject>Sulfonamides - pharmacology</subject><subject>Vertebrates: cardiovascular system</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1P3DAQhq0KVBban9DKFxAcTMdObCdHhGiLtIhD27Pl9Qe4SuzUTkDLr28CK1ayNJ7xM6-lB6EvFC4pUPGtAEBDRCWqc2AXAEI0hH9AKyo5JxWr-QFavSNH6LiUv3PLuaw_oiPKuBCUsRV6vkt26vQYUsTJ4_HR4cft4PKQOp3Dy-sD0WYMT3p0FpspZxdHfH7rL_Bmi43uTJh6rKNd7v0SFiKez5L0MIXoNBnCAy4hJqLHHHSHY7LuEzr0uivu866eoD_fb35f_yTr-x-311drYjjASDYN447XrWTWUAmibqSQrLJN2zhGG-r1Mqxb8My1lApfzaC1zoNoKsNpdYLO3nKHnP5NroyqD8W4rtPRpakoydq2BahnkL-BJqdSsvNqyKHXeasoqMW4-rXoVItOBUy9Gld83vu6-2Da9M7ut3aKZ-B0B-gyK_JZRxPKnqs5CClF9R8YsYli</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>RIGG, Lauren</creator><creator>MATTICK, Paul A. D</creator><creator>HEATH, Bronagh M</creator><creator>TERRAR, Derek A</creator><general>Oxford University Press</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><scope>7X8</scope></search><sort><creationdate>20030201</creationdate><title>Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node</title><author>RIGG, Lauren ; MATTICK, Paul A. D ; HEATH, Bronagh M ; TERRAR, Derek A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-b825e54972dc17064876723d898e2181fa7064490f2e9116f32dcddef0683c513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Benzylamines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Calcium - physiology</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors</topic><topic>Calmodulin - antagonists & inhibitors</topic><topic>Calmodulin - physiology</topic><topic>Cells, Cultured</topic><topic>Chelating Agents - pharmacology</topic><topic>Cyclic Nucleotide-Gated Cation Channels</topic><topic>Egtazic Acid - analogs & derivatives</topic><topic>Egtazic Acid - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guinea Pigs</topic><topic>Heart</topic><topic>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels</topic><topic>Ion Channel Gating - drug effects</topic><topic>Ion Channel Gating - physiology</topic><topic>Ion Channels - drug effects</topic><topic>Ion Channels - physiology</topic><topic>Male</topic><topic>Membrane Potentials - physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Potassium Channels</topic><topic>Protein Kinase Inhibitors</topic><topic>Sinoatrial Node - cytology</topic><topic>Sinoatrial Node - drug effects</topic><topic>Sinoatrial Node - physiology</topic><topic>Sulfonamides - pharmacology</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RIGG, Lauren</creatorcontrib><creatorcontrib>MATTICK, Paul A. D</creatorcontrib><creatorcontrib>HEATH, Bronagh M</creatorcontrib><creatorcontrib>TERRAR, Derek A</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><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RIGG, Lauren</au><au>MATTICK, Paul A. D</au><au>HEATH, Bronagh M</au><au>TERRAR, Derek A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>57</volume><issue>2</issue><spage>497</spage><epage>504</epage><pages>497-504</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (I(f)) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 degrees C) and the perforated patch voltage-clamp technique used to record I(f) activated by hyperpolarizing voltage steps. A 10-min loading of SA node cells with the calcium chelator BAPTA (using 10 microM BAPTA-AM) significantly reduced the amplitude of I(f) at all potentials studied (69+/-8% at -80 mV, n=6). BAPTA loading also shifted the voltage of half-activation (V(h)) of the conductance from -83+/-2 mV in control to -93+/-2 mV in BAPTA (n=6) without significantly altering the slope of activation. The calmodulin antagonists W-7 (10 microM), calmidazolium (25 microM) and ophiobolin A (20 microM) caused similar reductions in I(f) amplitude (73+/-4, 86+/-9 and 59+/-6% at -80 mV, n=6, 5 and 4, respectively) and shifts in V(h) (11+/-3, 14+/-3 and 8+/-2 mV). In cells pre-treated with W-7, exposure to BAPTA caused no further reduction in current amplitude (n=6). I(f) current amplitude was unaffected by the calmodulin dependent kinase (CaMKII) inhibitor KN-93 (1 microM) although this CaMKII inhibition did reduce L-type calcium by 48+/-19% at 0 mV (n=3). These results are consistent with a role for calcium and calmodulin in the regulation of I(f), via a mechanism that is independent of CaMKII. Alterations in intracellular calcium during the cardiac cycle may be involved in fine tuning the voltage-dependent properties of I(f) and may thus determine its relative contribution to pacemaking in the SA node.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12566122</pmid><doi>10.1016/s0008-6363(02)00668-5</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Benzylamines - pharmacology Biological and medical sciences Calcium - physiology Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors Calmodulin - antagonists & inhibitors Calmodulin - physiology Cells, Cultured Chelating Agents - pharmacology Cyclic Nucleotide-Gated Cation Channels Egtazic Acid - analogs & derivatives Egtazic Acid - pharmacology Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Guinea Pigs Heart Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Ion Channel Gating - drug effects Ion Channel Gating - physiology Ion Channels - drug effects Ion Channels - physiology Male Membrane Potentials - physiology Patch-Clamp Techniques Potassium Channels Protein Kinase Inhibitors Sinoatrial Node - cytology Sinoatrial Node - drug effects Sinoatrial Node - physiology Sulfonamides - pharmacology Vertebrates: cardiovascular system |
| title | Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node |
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