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This Article Full Text Full Text (PDF) All Versions of this Article: 574/2/349    most recent jphysiol.2006.110791v1 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by López-Domínguez, A. M. Articles by Cota, G. Search for Related Content PubMed PubMed Citation Articles by López-Domínguez, A. M. Articles by Cota, G. Related Collections Cellular

¹ Department of Physiology, Biophysics and Neurosciences
² Department of Biochemistry, Cinvestav-IPN, Mexico, DF 07000, Mexico

In clonal pituitary GH₃ cells, spontaneous action potentials drive the opening of Ca_v1 (L-type) channels, leading to Ca²⁺ transients that are coupled to prolactin gene transcription. Nerve growth factor (NGF) has been shown to stimulate prolactin synthesis by GH₃ cells, but the underlying mechanisms are unknown. Here we studied whether NGF influences prolactin gene expression and Ca²⁺ currents. By using RT-PCR, NGF (50 ng ml^–1) was found to augment prolactin mRNA levels by 80% when applied to GH₃ cells for 3 days. A parallel change in the prolactin content was detected by Western blotting. Both NGF-induced responses were mimicked by an agonist (Bay K 8644) and prevented by a blocker (nimodipine) of L-type channels. In whole-cell patch-clamp experiments, NGF enhanced the L-type Ca²⁺ current by 2-fold within 60 min. This effect reversed quickly upon growth factor withdrawal, but was maintained for days in the continued presence of NGF. In addition, chronic treatment ( 24 h) with NGF amplified the T-type current, which flows through Ca_v3 channels and is thought to support pacemaking activity. Thus, NGF probably increases the amount of Ca²⁺ that enters per action potential and may also induce a late increase in spike frequency. MC192, a specific antibody for the p75 neurotrophin receptor, but not tyrosine kinase inhibitors (K252a and lavendustin A), blocked the effects of NGF on Ca²⁺ currents. Overall, the results indicate that NGF activates the p75 receptor to cause a prolonged increase in Ca²⁺ influx through L-type channels, which in turn up-regulates the prolactin mRNA.

(Received 31 March 2006; accepted after revision 9 May 2006; first published online 11 May 2006)
Corresponding author G. Cota: Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN, AP 14-740, Mexico, DF 07000, Mexico. Email: gcota{at}fisio.cinvestav.mx