Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons
Previous reports revealed up-regulation of L-type high voltage-gated calcium channels (HVCCs) in mouse brains with ethanol physical dependence. We investigated mechanisms of enhancement of L-type HVCC function using mouse cerebrocortical neurons exposed to 50 mM ethanol for 3 days and the brains of...
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| Format: | Article |
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Elsevier
2006-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131934397X |
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| author | Masashi Katsura Masahiro Shibasaki Shinsuke Hayashida Fumiko Torigoe Atsushi Tsujimura Seitaro Ohkuma |
| author_facet | Masashi Katsura Masahiro Shibasaki Shinsuke Hayashida Fumiko Torigoe Atsushi Tsujimura Seitaro Ohkuma |
| author_sort | Masashi Katsura |
| collection | DOAJ |
| description | Previous reports revealed up-regulation of L-type high voltage-gated calcium channels (HVCCs) in mouse brains with ethanol physical dependence. We investigated mechanisms of enhancement of L-type HVCC function using mouse cerebrocortical neurons exposed to 50 mM ethanol for 3 days and the brains of mouse physically dependent on ethanol. Ethanol facilitated 30 mM KCl-stimulated 45Ca2+ influx in dose- and duration-dependent manners, which was abolished by nifedipine, an inhibitor specific to L-type HVCCs, but not by inhibitors for other types of HVCCs. Increase in [3H]PN200-110 binding to the particulate fractions from the ethanol-treated neurons was due to increased Bmax value with no changes in Kd value. Western blot analysis showed the increased expression of α1C, α1D, and α2/δ1 subunits with decreased β4 subunit expression and no changes in expressions of α1A, α1B, α1F, and α2 subunits. A similar pattern of the changes in the expression of these subunits of L-type HVCCs were observed in the cerebral cortex from mouse with ethanol physical dependence. These results indicate that sustained ethanol exposure to the neurons induces up-regulation of L-type HVCCs, which is due to increased expressions of α1C, α1D, and α2/δ1 subunits, and produces no alterations in P/Q- and N-type HVCC functions. Keywords:: ethanol (alcohol) physical dependence, high voltage-gated calcium channel, Ca2+ influx, [3H]PN200-110 binding, cerebral cortical neuron |
| first_indexed | 2024-12-10T13:11:50Z |
| format | Article |
| id | doaj.art-591f1ff096604c8482944f7e758e72f7 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T13:11:50Z |
| publishDate | 2006-01-01 |
| publisher | Elsevier |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-591f1ff096604c8482944f7e758e72f72022-12-22T01:47:38ZengElsevierJournal of Pharmacological Sciences1347-86132006-01-011022221230Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical NeuronsMasashi Katsura0Masahiro Shibasaki1Shinsuke Hayashida2Fumiko Torigoe3Atsushi Tsujimura4Seitaro Ohkuma5Department of Pharmacology, Kawasaki Medical University, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Pharmacology, Kawasaki Medical University, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Pharmacology, Kawasaki Medical University, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Pharmacology, Kawasaki Medical University, 577 Matsushima, Kurashiki 701-0192, JapanDepartment of Biochemistry and Molecular Genetics, Research Institute for Neurological Diseases and Geriatrics, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8401, JapanDepartment of Pharmacology, Kawasaki Medical University, 577 Matsushima, Kurashiki 701-0192, Japan; Correspondence author. sohkuma@bcc.kawasaki-m.ac.jpPrevious reports revealed up-regulation of L-type high voltage-gated calcium channels (HVCCs) in mouse brains with ethanol physical dependence. We investigated mechanisms of enhancement of L-type HVCC function using mouse cerebrocortical neurons exposed to 50 mM ethanol for 3 days and the brains of mouse physically dependent on ethanol. Ethanol facilitated 30 mM KCl-stimulated 45Ca2+ influx in dose- and duration-dependent manners, which was abolished by nifedipine, an inhibitor specific to L-type HVCCs, but not by inhibitors for other types of HVCCs. Increase in [3H]PN200-110 binding to the particulate fractions from the ethanol-treated neurons was due to increased Bmax value with no changes in Kd value. Western blot analysis showed the increased expression of α1C, α1D, and α2/δ1 subunits with decreased β4 subunit expression and no changes in expressions of α1A, α1B, α1F, and α2 subunits. A similar pattern of the changes in the expression of these subunits of L-type HVCCs were observed in the cerebral cortex from mouse with ethanol physical dependence. These results indicate that sustained ethanol exposure to the neurons induces up-regulation of L-type HVCCs, which is due to increased expressions of α1C, α1D, and α2/δ1 subunits, and produces no alterations in P/Q- and N-type HVCC functions. Keywords:: ethanol (alcohol) physical dependence, high voltage-gated calcium channel, Ca2+ influx, [3H]PN200-110 binding, cerebral cortical neuronhttp://www.sciencedirect.com/science/article/pii/S134786131934397X |
| spellingShingle | Masashi Katsura Masahiro Shibasaki Shinsuke Hayashida Fumiko Torigoe Atsushi Tsujimura Seitaro Ohkuma Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons Journal of Pharmacological Sciences |
| title | Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons |
| title_full | Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons |
| title_fullStr | Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons |
| title_full_unstemmed | Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons |
| title_short | Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons |
| title_sort | increase in expression of α1 and α2 δ1 subunits of l type high voltage gated calcium channels after sustained ethanol exposure in cerebral cortical neurons |
| url | http://www.sciencedirect.com/science/article/pii/S134786131934397X |
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