PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of IK in the anti-apoptotic action of PACAP.
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| Title: | PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of I |
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| Authors: | Mei, Y. A. (AUTHOR), Vaudry, D. (AUTHOR), Basille, M. (AUTHOR), Castel, H. (AUTHOR), Fournier, A. (AUTHOR), Vaudry, H. (AUTHOR), Gonzalez, B. J. (AUTHOR) |
| Source: | European Journal of Neuroscience. Mar2004, Vol. 19 Issue 6, p1446-1458. 13p. |
| Subjects: | Potassium channels, Peptides, Growth factors, Cell death, Phosphotransferases, Lyases |
| Abstract: | Activation of potassium (K+) currents plays a critical role in the control of programmed cell death. Because pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to inhibit the apoptotic cascade in the cerebellar cortex during development, we have investigated the effect of PACAP on K+ currents in cultured cerebellar granule cells using the patch-clamp technique in the whole-cell configuration. Two types of outward K+ currents, a transient K+ current ( IA) and a delayed rectifier K+ current ( IK) were characterized using two different voltage protocols and specific inhibitors of K+ channels. Application of PACAP induced a reversible reduction of the IK amplitude, but did not affect IA, while the PACAP-related peptide vasoactive intestinal polypeptide had no effect on either types of K+ currents. Repeated applications of PACAP induced gradual attenuation of the electrophysiological response. In the presence of guanosine 5′-[γthio]triphosphate (GTPγS), PACAP provoked a marked and irreversible IK depression, whereas cell dialysis with guanosine 5′-[βthio]diphosphate GDPβS totally abolished the effect of PACAP. Pre-treatment of the cells with pertussis toxin did not modify the effect of PACAP on IK. In contrast, cholera toxin suppressed the PACAP-induced inhibition of IK. Exposure of granule cells to dibutyryl cyclic adenosine monophosphate (dbcAMP) mimicked the inhibitory effect of PACAP on IK. Addition of the specific protein kinase A inhibitor H89 in the patch pipette solution prevented the reduction of IK induced by both PACAP and dbcAMP. PACAP provoked a sustained increase of the resting membrane potential in cerebellar granule cells cultured either in high or low KCl-containing medium, and this long-term depolarizing effect of PACAP was mimicked by the IK specific blocker tetraethylammonium chloride (TEA). In addition, pre-incubation of granule cells with TEA suppressed the effect of PACAP on resting membrane potential. TEA mimicked the neuroprotective effect of PACAP against ethanol-induced apoptotic cell death, and the increase of caspase-3 activity observed after exposure of granule cells to ethanol was also significantly inhibited by TEA. Taken together, the present results demonstrate that, in rat cerebellar granule cells, PACAP reduces the delayed outward rectifier K+ current by activating a type 1 PACAP (PAC1) receptor coupled to the adenylyl cyclase/protein kinase A pathway through a cholera toxin-sensitive Gs protein. Our data also show that PACAP and TEA induce long-term depolarization of the resting membrane potential, promote cell survival and inhibit caspase-3 activity, suggesting that PACAP-evoked inhibition of IK contributes to the anti-apoptotic effect of the peptide on cerebellar granule cells. [ABSTRACT FROM AUTHOR] |
| Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 12725227 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of I<subscript>K</subscript> in the anti-apoptotic action of PACAP. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Mei%2C+Y%2E+A%2E%22">Mei, Y. A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vaudry%2C+D%2E%22">Vaudry, D.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Basille%2C+M%2E%22">Basille, M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Castel%2C+H%2E%22">Castel, H.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fournier%2C+A%2E%22">Fournier, A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vaudry%2C+H%2E%22">Vaudry, H.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gonzalez%2C+B%2E+J%2E%22">Gonzalez, B. J.</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Mar2004, Vol. 19 Issue 6, p1446-1458. 13p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Potassium+channels%22">Potassium channels</searchLink><br /><searchLink fieldCode="DE" term="%22Peptides%22">Peptides</searchLink><br /><searchLink fieldCode="DE" term="%22Growth+factors%22">Growth factors</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+death%22">Cell death</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphotransferases%22">Phosphotransferases</searchLink><br /><searchLink fieldCode="DE" term="%22Lyases%22">Lyases</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Activation of potassium (K+) currents plays a critical role in the control of programmed cell death. Because pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to inhibit the apoptotic cascade in the cerebellar cortex during development, we have investigated the effect of PACAP on K+ currents in cultured cerebellar granule cells using the patch-clamp technique in the whole-cell configuration. Two types of outward K+ currents, a transient K+ current ( IA) and a delayed rectifier K+ current ( IK) were characterized using two different voltage protocols and specific inhibitors of K+ channels. Application of PACAP induced a reversible reduction of the IK amplitude, but did not affect IA, while the PACAP-related peptide vasoactive intestinal polypeptide had no effect on either types of K+ currents. Repeated applications of PACAP induced gradual attenuation of the electrophysiological response. In the presence of guanosine 5′-[γthio]triphosphate (GTPγS), PACAP provoked a marked and irreversible IK depression, whereas cell dialysis with guanosine 5′-[βthio]diphosphate GDPβS totally abolished the effect of PACAP. Pre-treatment of the cells with pertussis toxin did not modify the effect of PACAP on IK. In contrast, cholera toxin suppressed the PACAP-induced inhibition of IK. Exposure of granule cells to dibutyryl cyclic adenosine monophosphate (dbcAMP) mimicked the inhibitory effect of PACAP on IK. Addition of the specific protein kinase A inhibitor H89 in the patch pipette solution prevented the reduction of IK induced by both PACAP and dbcAMP. PACAP provoked a sustained increase of the resting membrane potential in cerebellar granule cells cultured either in high or low KCl-containing medium, and this long-term depolarizing effect of PACAP was mimicked by the IK specific blocker tetraethylammonium chloride (TEA). In addition, pre-incubation of granule cells with TEA suppressed the effect of PACAP on resting membrane potential. TEA mimicked the neuroprotective effect of PACAP against ethanol-induced apoptotic cell death, and the increase of caspase-3 activity observed after exposure of granule cells to ethanol was also significantly inhibited by TEA. Taken together, the present results demonstrate that, in rat cerebellar granule cells, PACAP reduces the delayed outward rectifier K+ current by activating a type 1 PACAP (PAC1) receptor coupled to the adenylyl cyclase/protein kinase A pathway through a cholera toxin-sensitive Gs protein. Our data also show that PACAP and TEA induce long-term depolarization of the resting membrane potential, promote cell survival and inhibit caspase-3 activity, suggesting that PACAP-evoked inhibition of IK contributes to the anti-apoptotic effect of the peptide on cerebellar granule cells. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1111/j.1460-9568.2004.03227.x Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 1446 Subjects: – SubjectFull: Potassium channels Type: general – SubjectFull: Peptides Type: general – SubjectFull: Growth factors Type: general – SubjectFull: Cell death Type: general – SubjectFull: Phosphotransferases Type: general – SubjectFull: Lyases Type: general Titles: – TitleFull: PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of IK in the anti-apoptotic action of PACAP. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Mei, Y. A. – PersonEntity: Name: NameFull: Vaudry, D. – PersonEntity: Name: NameFull: Basille, M. – PersonEntity: Name: NameFull: Castel, H. – PersonEntity: Name: NameFull: Fournier, A. – PersonEntity: Name: NameFull: Vaudry, H. – PersonEntity: Name: NameFull: Gonzalez, B. J. IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 03 Text: Mar2004 Type: published Y: 2004 Identifiers: – Type: issn-print Value: 0953816X Numbering: – Type: volume Value: 19 – Type: issue Value: 6 Titles: – TitleFull: European Journal of Neuroscience Type: main |
| ResultId | 1 |
