Eintrag weiter verarbeiten
M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades
Gespeichert in:
| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | The Journal of Neuroscience, 26, 2006, 45, S. 11588-11598 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
|
| Schlagwörter: |
| author_facet |
Liu, Liwang Zhao, Rubing Bai, Yan Stanish, Lee F. Evans, James E. Sanderson, Michael J. Bonventre, Joseph V. Rittenhouse, Ann R. Liu, Liwang Zhao, Rubing Bai, Yan Stanish, Lee F. Evans, James E. Sanderson, Michael J. Bonventre, Joseph V. Rittenhouse, Ann R. |
|---|---|
| author |
Liu, Liwang Zhao, Rubing Bai, Yan Stanish, Lee F. Evans, James E. Sanderson, Michael J. Bonventre, Joseph V. Rittenhouse, Ann R. |
| spellingShingle |
Liu, Liwang Zhao, Rubing Bai, Yan Stanish, Lee F. Evans, James E. Sanderson, Michael J. Bonventre, Joseph V. Rittenhouse, Ann R. The Journal of Neuroscience M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades General Neuroscience |
| author_sort |
liu, liwang |
| spelling |
Liu, Liwang Zhao, Rubing Bai, Yan Stanish, Lee F. Evans, James E. Sanderson, Michael J. Bonventre, Joseph V. Rittenhouse, Ann R. 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2102-06.2006 <jats:p>Ion channels reside in a sea of phospholipids. During normal fluctuations in membrane potential and periods of modulation, lipids that directly associate with channel proteins influence gating by incompletely understood mechanisms. In one model, M<jats:sub>1</jats:sub>-muscarinic receptors (M<jats:sub>1</jats:sub>Rs) may inhibit both Ca<jats:sup>2+</jats:sup>(L- and N-) and K<jats:sup>+</jats:sup>(M-) currents by losing a putative interaction between channels and phosphatidylinositol-4,5-bisphosphate (PIP<jats:sub>2</jats:sub>). However, we found previously that M<jats:sub>1</jats:sub>R inhibition of N-current in superior cervical ganglion (SCG) neurons requires loss of PIP<jats:sub>2</jats:sub>and generation of a free fatty acid, probably arachidonic acid (AA) by phospholipase A<jats:sub>2</jats:sub>(PLA<jats:sub>2</jats:sub>). It is not known whether PLA<jats:sub>2</jats:sub>activity and AA also participate in L- and M-current modulation in SCG neurons. To test whether PLA<jats:sub>2</jats:sub>plays a similar role in M<jats:sub>1</jats:sub>R inhibition of L- and M-currents, we used several experimental approaches and found unanticipated divergent signaling. First, blocking resynthesis of PIP<jats:sub>2</jats:sub>minimized M-current recovery from inhibition, whereas L-current recovered normally. Second, L-current inhibition required group IVa PLA<jats:sub>2</jats:sub>[cytoplasmic PLA<jats:sub>2</jats:sub>(cPLA<jats:sub>2</jats:sub>)], whereas M-current did not. Western blot and imaging studies confirmed acute activation of cPLA<jats:sub>2</jats:sub>by muscarinic stimulation. Third, in type IIa PLA<jats:sub>2</jats:sub>[secreted (<jats:italic>sPLA<jats:sub>2</jats:sub></jats:italic>)]<jats:sup>−/−</jats:sup>/<jats:italic>cPLA</jats:italic><jats:sub arrange="stagger"><jats:italic>2</jats:italic></jats:sub><jats:sup arrange="stagger">−/−</jats:sup>double-knock-out SCG neurons, muscarinic inhibition of L-current decreased. In contrast, M-current inhibition remained unaffected but recovery was impaired. Our results indicate that L-current is inhibited by a pathway previously shown to control M-current over-recovery after washout of muscarinic agonist. Our findings support a model of M<jats:sub>1</jats:sub>R-meditated channel modulation that broadens rather than restricts the roles of phospholipids and fatty acids in regulating ion channel activity.</jats:p> M<sub>1</sub>Muscarinic Receptors Inhibit L-type Ca<sup>2+</sup>Current and M-Current by Divergent Signal Transduction Cascades The Journal of Neuroscience |
| doi_str_mv |
10.1523/jneurosci.2102-06.2006 |
| facet_avail |
Online Free |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTUyMy9qbmV1cm9zY2kuMjEwMi0wNi4yMDA2 |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTUyMy9qbmV1cm9zY2kuMjEwMi0wNi4yMDA2 |
| institution |
DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 |
| imprint |
Society for Neuroscience, 2006 |
| imprint_str_mv |
Society for Neuroscience, 2006 |
| issn |
0270-6474 1529-2401 |
| issn_str_mv |
0270-6474 1529-2401 |
| language |
English |
| mega_collection |
Society for Neuroscience (CrossRef) |
| match_str |
liu2006m1muscarinicreceptorsinhibitltypeca2currentandmcurrentbydivergentsignaltransductioncascades |
| publishDateSort |
2006 |
| publisher |
Society for Neuroscience |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Neuroscience |
| source_id |
49 |
| title |
M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_unstemmed |
M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_full |
M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_fullStr |
M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_full_unstemmed |
M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_short |
M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_sort |
m<sub>1</sub>muscarinic receptors inhibit l-type ca<sup>2+</sup>current and m-current by divergent signal transduction cascades |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.2102-06.2006 |
| publishDate |
2006 |
| physical |
11588-11598 |
| description |
<jats:p>Ion channels reside in a sea of phospholipids. During normal fluctuations in membrane potential and periods of modulation, lipids that directly associate with channel proteins influence gating by incompletely understood mechanisms. In one model, M<jats:sub>1</jats:sub>-muscarinic receptors (M<jats:sub>1</jats:sub>Rs) may inhibit both Ca<jats:sup>2+</jats:sup>(L- and N-) and K<jats:sup>+</jats:sup>(M-) currents by losing a putative interaction between channels and phosphatidylinositol-4,5-bisphosphate (PIP<jats:sub>2</jats:sub>). However, we found previously that M<jats:sub>1</jats:sub>R inhibition of N-current in superior cervical ganglion (SCG) neurons requires loss of PIP<jats:sub>2</jats:sub>and generation of a free fatty acid, probably arachidonic acid (AA) by phospholipase A<jats:sub>2</jats:sub>(PLA<jats:sub>2</jats:sub>). It is not known whether PLA<jats:sub>2</jats:sub>activity and AA also participate in L- and M-current modulation in SCG neurons. To test whether PLA<jats:sub>2</jats:sub>plays a similar role in M<jats:sub>1</jats:sub>R inhibition of L- and M-currents, we used several experimental approaches and found unanticipated divergent signaling. First, blocking resynthesis of PIP<jats:sub>2</jats:sub>minimized M-current recovery from inhibition, whereas L-current recovered normally. Second, L-current inhibition required group IVa PLA<jats:sub>2</jats:sub>[cytoplasmic PLA<jats:sub>2</jats:sub>(cPLA<jats:sub>2</jats:sub>)], whereas M-current did not. Western blot and imaging studies confirmed acute activation of cPLA<jats:sub>2</jats:sub>by muscarinic stimulation. Third, in type IIa PLA<jats:sub>2</jats:sub>[secreted (<jats:italic>sPLA<jats:sub>2</jats:sub></jats:italic>)]<jats:sup>−/−</jats:sup>/<jats:italic>cPLA</jats:italic><jats:sub arrange="stagger"><jats:italic>2</jats:italic></jats:sub><jats:sup arrange="stagger">−/−</jats:sup>double-knock-out SCG neurons, muscarinic inhibition of L-current decreased. In contrast, M-current inhibition remained unaffected but recovery was impaired. Our results indicate that L-current is inhibited by a pathway previously shown to control M-current over-recovery after washout of muscarinic agonist. Our findings support a model of M<jats:sub>1</jats:sub>R-meditated channel modulation that broadens rather than restricts the roles of phospholipids and fatty acids in regulating ion channel activity.</jats:p> |
| container_issue |
45 |
| container_start_page |
11588 |
| container_title |
The Journal of Neuroscience |
| container_volume |
26 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792335792250552323 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T14:49:38.523Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=M1Muscarinic+Receptors+Inhibit+L-type+Ca2%2BCurrent+and+M-Current+by+Divergent+Signal+Transduction+Cascades&rft.date=2006-11-08&genre=article&issn=1529-2401&volume=26&issue=45&spage=11588&epage=11598&pages=11588-11598&jtitle=The+Journal+of+Neuroscience&atitle=M%3Csub%3E1%3C%2Fsub%3EMuscarinic+Receptors+Inhibit+L-type+Ca%3Csup%3E2%2B%3C%2Fsup%3ECurrent+and+M-Current+by+Divergent+Signal+Transduction+Cascades&aulast=Rittenhouse&aufirst=Ann+R.&rft_id=info%3Adoi%2F10.1523%2Fjneurosci.2102-06.2006&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792335792250552323 |
| author | Liu, Liwang, Zhao, Rubing, Bai, Yan, Stanish, Lee F., Evans, James E., Sanderson, Michael J., Bonventre, Joseph V., Rittenhouse, Ann R. |
| author_facet | Liu, Liwang, Zhao, Rubing, Bai, Yan, Stanish, Lee F., Evans, James E., Sanderson, Michael J., Bonventre, Joseph V., Rittenhouse, Ann R., Liu, Liwang, Zhao, Rubing, Bai, Yan, Stanish, Lee F., Evans, James E., Sanderson, Michael J., Bonventre, Joseph V., Rittenhouse, Ann R. |
| author_sort | liu, liwang |
| container_issue | 45 |
| container_start_page | 11588 |
| container_title | The Journal of Neuroscience |
| container_volume | 26 |
| description | <jats:p>Ion channels reside in a sea of phospholipids. During normal fluctuations in membrane potential and periods of modulation, lipids that directly associate with channel proteins influence gating by incompletely understood mechanisms. In one model, M<jats:sub>1</jats:sub>-muscarinic receptors (M<jats:sub>1</jats:sub>Rs) may inhibit both Ca<jats:sup>2+</jats:sup>(L- and N-) and K<jats:sup>+</jats:sup>(M-) currents by losing a putative interaction between channels and phosphatidylinositol-4,5-bisphosphate (PIP<jats:sub>2</jats:sub>). However, we found previously that M<jats:sub>1</jats:sub>R inhibition of N-current in superior cervical ganglion (SCG) neurons requires loss of PIP<jats:sub>2</jats:sub>and generation of a free fatty acid, probably arachidonic acid (AA) by phospholipase A<jats:sub>2</jats:sub>(PLA<jats:sub>2</jats:sub>). It is not known whether PLA<jats:sub>2</jats:sub>activity and AA also participate in L- and M-current modulation in SCG neurons. To test whether PLA<jats:sub>2</jats:sub>plays a similar role in M<jats:sub>1</jats:sub>R inhibition of L- and M-currents, we used several experimental approaches and found unanticipated divergent signaling. First, blocking resynthesis of PIP<jats:sub>2</jats:sub>minimized M-current recovery from inhibition, whereas L-current recovered normally. Second, L-current inhibition required group IVa PLA<jats:sub>2</jats:sub>[cytoplasmic PLA<jats:sub>2</jats:sub>(cPLA<jats:sub>2</jats:sub>)], whereas M-current did not. Western blot and imaging studies confirmed acute activation of cPLA<jats:sub>2</jats:sub>by muscarinic stimulation. Third, in type IIa PLA<jats:sub>2</jats:sub>[secreted (<jats:italic>sPLA<jats:sub>2</jats:sub></jats:italic>)]<jats:sup>−/−</jats:sup>/<jats:italic>cPLA</jats:italic><jats:sub arrange="stagger"><jats:italic>2</jats:italic></jats:sub><jats:sup arrange="stagger">−/−</jats:sup>double-knock-out SCG neurons, muscarinic inhibition of L-current decreased. In contrast, M-current inhibition remained unaffected but recovery was impaired. Our results indicate that L-current is inhibited by a pathway previously shown to control M-current over-recovery after washout of muscarinic agonist. Our findings support a model of M<jats:sub>1</jats:sub>R-meditated channel modulation that broadens rather than restricts the roles of phospholipids and fatty acids in regulating ion channel activity.</jats:p> |
| doi_str_mv | 10.1523/jneurosci.2102-06.2006 |
| facet_avail | Online, Free |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTUyMy9qbmV1cm9zY2kuMjEwMi0wNi4yMDA2 |
| imprint | Society for Neuroscience, 2006 |
| imprint_str_mv | Society for Neuroscience, 2006 |
| institution | DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3 |
| issn | 0270-6474, 1529-2401 |
| issn_str_mv | 0270-6474, 1529-2401 |
| language | English |
| last_indexed | 2024-03-01T14:49:38.523Z |
| match_str | liu2006m1muscarinicreceptorsinhibitltypeca2currentandmcurrentbydivergentsignaltransductioncascades |
| mega_collection | Society for Neuroscience (CrossRef) |
| physical | 11588-11598 |
| publishDate | 2006 |
| publishDateSort | 2006 |
| publisher | Society for Neuroscience |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Neuroscience |
| source_id | 49 |
| spelling | Liu, Liwang Zhao, Rubing Bai, Yan Stanish, Lee F. Evans, James E. Sanderson, Michael J. Bonventre, Joseph V. Rittenhouse, Ann R. 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2102-06.2006 <jats:p>Ion channels reside in a sea of phospholipids. During normal fluctuations in membrane potential and periods of modulation, lipids that directly associate with channel proteins influence gating by incompletely understood mechanisms. In one model, M<jats:sub>1</jats:sub>-muscarinic receptors (M<jats:sub>1</jats:sub>Rs) may inhibit both Ca<jats:sup>2+</jats:sup>(L- and N-) and K<jats:sup>+</jats:sup>(M-) currents by losing a putative interaction between channels and phosphatidylinositol-4,5-bisphosphate (PIP<jats:sub>2</jats:sub>). However, we found previously that M<jats:sub>1</jats:sub>R inhibition of N-current in superior cervical ganglion (SCG) neurons requires loss of PIP<jats:sub>2</jats:sub>and generation of a free fatty acid, probably arachidonic acid (AA) by phospholipase A<jats:sub>2</jats:sub>(PLA<jats:sub>2</jats:sub>). It is not known whether PLA<jats:sub>2</jats:sub>activity and AA also participate in L- and M-current modulation in SCG neurons. To test whether PLA<jats:sub>2</jats:sub>plays a similar role in M<jats:sub>1</jats:sub>R inhibition of L- and M-currents, we used several experimental approaches and found unanticipated divergent signaling. First, blocking resynthesis of PIP<jats:sub>2</jats:sub>minimized M-current recovery from inhibition, whereas L-current recovered normally. Second, L-current inhibition required group IVa PLA<jats:sub>2</jats:sub>[cytoplasmic PLA<jats:sub>2</jats:sub>(cPLA<jats:sub>2</jats:sub>)], whereas M-current did not. Western blot and imaging studies confirmed acute activation of cPLA<jats:sub>2</jats:sub>by muscarinic stimulation. Third, in type IIa PLA<jats:sub>2</jats:sub>[secreted (<jats:italic>sPLA<jats:sub>2</jats:sub></jats:italic>)]<jats:sup>−/−</jats:sup>/<jats:italic>cPLA</jats:italic><jats:sub arrange="stagger"><jats:italic>2</jats:italic></jats:sub><jats:sup arrange="stagger">−/−</jats:sup>double-knock-out SCG neurons, muscarinic inhibition of L-current decreased. In contrast, M-current inhibition remained unaffected but recovery was impaired. Our results indicate that L-current is inhibited by a pathway previously shown to control M-current over-recovery after washout of muscarinic agonist. Our findings support a model of M<jats:sub>1</jats:sub>R-meditated channel modulation that broadens rather than restricts the roles of phospholipids and fatty acids in regulating ion channel activity.</jats:p> M<sub>1</sub>Muscarinic Receptors Inhibit L-type Ca<sup>2+</sup>Current and M-Current by Divergent Signal Transduction Cascades The Journal of Neuroscience |
| spellingShingle | Liu, Liwang, Zhao, Rubing, Bai, Yan, Stanish, Lee F., Evans, James E., Sanderson, Michael J., Bonventre, Joseph V., Rittenhouse, Ann R., The Journal of Neuroscience, M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades, General Neuroscience |
| title | M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_full | M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_fullStr | M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_full_unstemmed | M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_short | M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| title_sort | m<sub>1</sub>muscarinic receptors inhibit l-type ca<sup>2+</sup>current and m-current by divergent signal transduction cascades |
| title_unstemmed | M1Muscarinic Receptors Inhibit L-type Ca2+Current and M-Current by Divergent Signal Transduction Cascades |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.2102-06.2006 |