Comparison of adenosine triphosphate‐ and nicotine‐activated inward currents in rat phaeochromocytoma cells.

K. Nakazawa, K. Fujimori, A. Takanaka, Kazuhide Inoue

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Abstract

1. The adenosine triphosphate (ATP)‐activated inward current was compared to the nicotine‐activated inward current in nerve growth factor (NGF)‐treated rat phaeochromocytoma PC12 cells. 2. Both ATP and nicotine activated an inward current at negative holding potentials. The concentration of ATP necessary to activate the inward current was about 10‐fold higher than that of nicotine; the EC50 was 20.5 microM for ATP and 2.4 microM for nicotine. The maximal responses induced by ATP and nicotine were almost identical in the same cells. The current‐voltage relationship for the ATP‐activated current was very similar to that for the nicotine‐activated current, and both currents reversed around 0 mV in a physiological saline. 3. The ATP‐activated current and the nicotine‐activated current were not additive; the current activated by a combined administration of ATP (100 microM) and nicotine (10 microM) was only about 20% larger than the current activated by either ATP or nicotine alone. Nicotine (100 microM) did not increase the current activated by 1 microM‐ATP. 4. ATP could activate an inward current in the cells even after desensitization to nicotine had developed. 5. Hexamethonium (100 microM) selectively blocked the nicotine‐activated current whereas suramin (100 microM), a purinoceptor antagonist, selectively blocked the ATP‐activated current. 6. Ionic selectivity was studied by changing compositions of extracellular solutions. When external Na+ was replaced with Cs+, both ATP and nicotine activated inward currents. However, with an extracellular solution containing Tris or glucosamine as a major cation, only ATP, not nicotine, activated an inward current. 7. ATP‐ and nicotine‐activated currents were also recorded from cells bathed in a solution containing 1.8 mM‐Ca2+ as the only external cation, suggesting that both pathways are Ca2+ permeable. 8. The results suggest that the ATP‐sensitive ionic pathway is not independent of the nicotine‐sensitive pathway in these cells. Our working hypothesis is that ATP and nicotine activate the same channels but the binding sites and the open‐states of the channels are different between these two agonists.

Original languageEnglish
Pages (from-to)647-660
Number of pages14
JournalThe Journal of Physiology
Volume434
Issue number1
DOIs
Publication statusPublished - Mar 1 1991

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Pheochromocytoma
Nicotine
Adenosine Triphosphate
Cations
Purinergic Antagonists
Suramin
Hexamethonium
PC12 Cells
Glucosamine
Nerve Growth Factor
Binding Sites

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Comparison of adenosine triphosphate‐ and nicotine‐activated inward currents in rat phaeochromocytoma cells. / Nakazawa, K.; Fujimori, K.; Takanaka, A.; Inoue, Kazuhide.

In: The Journal of Physiology, Vol. 434, No. 1, 01.03.1991, p. 647-660.

Research output: Contribution to journalArticle

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abstract = "1. The adenosine triphosphate (ATP)‐activated inward current was compared to the nicotine‐activated inward current in nerve growth factor (NGF)‐treated rat phaeochromocytoma PC12 cells. 2. Both ATP and nicotine activated an inward current at negative holding potentials. The concentration of ATP necessary to activate the inward current was about 10‐fold higher than that of nicotine; the EC50 was 20.5 microM for ATP and 2.4 microM for nicotine. The maximal responses induced by ATP and nicotine were almost identical in the same cells. The current‐voltage relationship for the ATP‐activated current was very similar to that for the nicotine‐activated current, and both currents reversed around 0 mV in a physiological saline. 3. The ATP‐activated current and the nicotine‐activated current were not additive; the current activated by a combined administration of ATP (100 microM) and nicotine (10 microM) was only about 20{\%} larger than the current activated by either ATP or nicotine alone. Nicotine (100 microM) did not increase the current activated by 1 microM‐ATP. 4. ATP could activate an inward current in the cells even after desensitization to nicotine had developed. 5. Hexamethonium (100 microM) selectively blocked the nicotine‐activated current whereas suramin (100 microM), a purinoceptor antagonist, selectively blocked the ATP‐activated current. 6. Ionic selectivity was studied by changing compositions of extracellular solutions. When external Na+ was replaced with Cs+, both ATP and nicotine activated inward currents. However, with an extracellular solution containing Tris or glucosamine as a major cation, only ATP, not nicotine, activated an inward current. 7. ATP‐ and nicotine‐activated currents were also recorded from cells bathed in a solution containing 1.8 mM‐Ca2+ as the only external cation, suggesting that both pathways are Ca2+ permeable. 8. The results suggest that the ATP‐sensitive ionic pathway is not independent of the nicotine‐sensitive pathway in these cells. Our working hypothesis is that ATP and nicotine activate the same channels but the binding sites and the open‐states of the channels are different between these two agonists.",
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