This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaneishi, K. Articles by Kato, M. Search for Related Content PubMed PubMed Citation Articles by Kaneishi, K. Articles by Kato, M.

3',5'-Cyclic Adenosine Monophosphate Augments Intracellular Ca²⁺ Concentration and Gonadotropin-Releasing Hormone (GnRH) Release in Immortalized GnRH Neurons in an Na⁺-Dependent Manner

Department of Physiology, Nippon Medical School (K.K., Y.S., M.K.), Tokyo 113-8602, Japan; and Institute for Molecular and Cellular Regulation, Gunma University (H.K.), Maebashi 371-8511, Japan

Address all correspondence and requests for reprints to: Dr. Masakatsu Kato, Department of Physiology, Nippon Medical School, Sendagi 1, Bunkyo, Tokyo 113-8602, Japan. E-mail: mkato{at}nms.ac.jp.

In GT1-7 cells, cAMP increases the intracellular Ca²⁺ concentration ([Ca²⁺]_i) through activation of the voltage-gated Ca²⁺ channels, thereby facilitating GnRH release. To activate these channels, the membrane potential must be depolarized. In the present study we hypothesize that cAMP depolarizes the cells by increasing the membrane Na⁺ permeability, as in the case of somatotrophs and pancreatic ß-cells. To examine this, we analyzed [Ca²⁺]_i and [Na⁺]_i in GT1-7 cells by an intracellular ion-imaging technique along with cAMP assay by RIA.

Forskolin, a direct activator of adenylyl cyclase, increased [Ca²⁺]_i and [Na⁺]_i via cAMP formation. The forskolin-induced increase in [Ca²⁺]_i depended on the presence of Ca²⁺ and Na⁺ in the extracellular solution. This response was blocked by the voltage-gated Ca²⁺ channel blocker, nifedipine; the nonselective cation channel blocker, gadolinium (Gd³⁺); and the cyclic nucleotide-gated channel blocker, l-cis-diltiazem. In contrast, the forskolin-induced increase in [Na⁺]_i depended only on extracellular Na⁺, not on Ca²⁺. Gd³⁺ and l-cis-diltiazem also blocked the increase in [Na⁺]_i. Furthermore, the forskolin-induced increase in GnRH release was blunted in both low Ca²⁺ and low Na⁺ media. The results indicate that cAMP increases the membrane Na⁺ permeability, probably through nonselective cation channels on GT1-7 cells, thereby promoting GnRH release.

This article has been cited by other articles:

				S. Constantin and S. Wray Gonadotropin-Releasing Hormone-1 Neuronal Activity Is Independent of Cyclic Nucleotide-Gated Channels Endocrinology, January 1, 2008; 149(1): 279 - 290. [Abstract] [Full Text] [PDF]

				P. Smolen, D. A. Baxter, and J. H. Byrne A Model of the Roles of Essential Kinases in the Induction and Expression of Late Long-Term Potentiation Biophys. J., April 15, 2006; 90(8): 2760 - 2775. [Abstract] [Full Text] [PDF]

				E. C. Chen, M. A. Javors, C. Norris, T. Siler-Khodr, R. S. Schenken, and T. S. King Dependence of 3',5'-Cyclic Adenosine Monophosphate--Stimulated Gonadotropin-Releasing Hormone Release on Intracellular Calcium Channels in Superfused GT1-7 Neurons Reproductive Sciences, September 1, 2004; 11(6): 393 - 398. [Abstract] [PDF]