The molecular mechanism underlying pentylenetetrazole-induced bursting activity in Euhadra neurons: involvement of protein phosphorylation
| Autor: | Ozono Satoru, Onozuka Minoru, Kubo Kin-Ya |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Pharmacology
biology Chemistry medicine.drug_class Immunology Membrane hyperpolarization Hyperpolarization (biology) Protein kinase inhibitor biology.organism_classification Molecular biology Euhadra Euhadra peliomphala Ca2+/calmodulin-dependent protein kinase Biophysics medicine Protein kinase A Protein kinase C |
| Zdroj: | Comparative Biochemistry and Physiology Part C: Comparative Pharmacology. 100:423-432 |
| ISSN: | 0306-4492 |
| DOI: | 10.1016/0742-8413(91)90019-p |
| Popis: | 1. The involvement of protein phosphorylation in the pentylenetetrazole (PTZ)-induced bursting activity (BA) was evaluated in identified neurons of the snail. Euhadra peliomphala by examining the effect of various protein kinases and their inhibitors on the membrane properties induced by PTZ. 2. In neurons which normally exhibited spontaneous regular firing, PTZ elicited BA, the negative slope resistance (NSR) in the steady-state current ( I )-voltage ( V ) relationship and a reduction of the delayed potassium current ( I KD ) in a dose-dependent manner. These were inhibited by the cAMP-dependent protein kinase inhibitors, protein kinase inhibitor isolated from rabbit muscle and N -[2-(methylamino) ethyl]-5-isoquinolinesulfonamide. 3. Intracellular injection of catalytic subunit (CS) of cAMP-dependent protein kinase enhanced PTZ-induced NSR and reduction of I kd , as well as a conversion of the BA to a long-lasting depolarization of the membrane, whereas a saturating dose of the CS occluded PTZ action on the NSR and I KD . 4. Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), when intracellularly injected during the depolarizing phase of PTZ-induced bursting cycle, changed to a prolonged hyperpolarization of the membrane. This kinase also restored the PTZ-suppressed I KD nearly to the pre-PTZ level. However, when intracellular injection of CaMKII and application of N -(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide, a calmodulin inhibitor, to the inside and outside of the neuron were simultaneously carried out, neither post-burst hyperpolarization nor restoration of the I KD was observed. 5. Intracellular injection of calmodulin, together with calcium chloride, had little effect on both the BA and reduction of I KD induced by PTZ. 6. Simultaneous application of 40 μM 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, which selectively suppressed the phosphatidylserine-dependent protein phosphorylation in extracts from Euhadra ganglia, to both the inside and outside of the neuron, did not produce any significant change in the membrane properties induced by PTX. Intracellular injection of protein kinase C also brought about no effect. 7. These findings suggest that PTZ stimulates cAMP-dependent protein phosphorylation which, in turn, is involved in the development of NSR and reduction of I KD , leading to the depolarization of the membrane. In addition, we propose that the Ca 2+ ions, increased during the depolarizing phase of the BA cycle, form a Ca 2+ /calmodulin complex and subsequent protein phosphorylation, coupled with the opening of potassium channels, leading to the membrane hyperpolarization. |
| Databáze: | OpenAIRE |
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