HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 566/3/717    most recent jphysiol.2005.085803v1 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Miranda, P. Articles by Barros, F. Search for Related Content PubMed PubMed Citation Articles by Miranda, P. Articles by Barros, F.

¹ Departamento de Bioquímica y Biología Molecular, Edificio Santiago Gascón, Campus del Cristo, Universidad de Oviedo, E-33006, Oviedo, Asturias, Spain

The identity of the G-protein coupling thyrotropin-releasing hormone (TRH) receptors to rat ether-à-go-go related gene (r-ERG) K⁺ channel modulation was studied in situ using perforated-patch clamped adenohypophysial GH₃ cells and dominant-negative variants (G-QL/DN) of G-protein subunits. Expression of dominant-negative G_q/11 that minimizes the TRH-induced Ca²⁺ signal had no effect on r-ERG current inhibition elicited by the hormone. In contrast, the introduction of dominant-negative variants of G₁₃ and the small G-protein Rho caused a significant loss of the inhibitory effect of TRH on r-ERG. A strong reduction of this TRH effect was also obtained in cells expressing either dominant-negative G_s or transducin subunits, an agent known to sequester free G-protein ß dimers. As a further indication of specificity of the dominant-negative effects, only the dominant-negative variants of G₁₃ and Rho (but not G_s-QL/DN or G_t) were able to reduce the TRH-induced shifts of human ERG (HERG) activation voltage dependence in HEK293 cells permanently expressing HERG channels and TRH receptors. Our results demonstrate that whereas the TRH receptor uses a G_q/11 protein for transducing the Ca²⁺ signal during the initial response to TRH, this G-protein is not involved in the TRH-induced inhibition of endogenous r-ERG currents in pituitary cells. They also identify G_s (or a G_s-like protein) and G₁₃ as important contributors to the hormonal effect in these cells and suggest that ß dimers released from these proteins may participate in modulation of ERG currents triggered by TRH.

(Received 28 February 2005; accepted after revision 12 May 2005; first published online 19 May 2005)
Corresponding author F. Barros: Departamento de Bioquímica y Biología Molecular, Edificio Santiago Gascón, Campus del Cristo, Universidad de Oviedo, E-33006, Oviedo, Asturias, Spain. Email: fbarros{at}correo.uniovi.es

This article has been cited by other articles:

				C. Alonso-Ron, P. de la Pena, P. Miranda, P. Dominguez, and F. Barros Thermodynamic and Kinetic Properties of Amino-Terminal and S4-S5 Loop HERG Channel Mutants under Steady-State Conditions Biophys. J., May 15, 2008; 94(10): 3893 - 3911. [Abstract] [Full Text] [PDF]

				X. Wang, G. H. Hockerman, H. W. Green III, C. F. Babbs, S. I. Mohammad, D. Gerrard, M. A. Latour, B. London, K. M. Hannon, and A. L. Pond Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway FASEB J, July 1, 2006; 20(9): 1531 - 1533. [Abstract] [Full Text] [PDF]

				N. M. Kirchberger, I. Wulfsen, J. R. Schwarz, and C. K. Bauer Effects of TRH on heteromeric rat erg1a/1b K+ channels are dominated by the rerg1b subunit J. Physiol., February 15, 2006; 571(1): 27 - 42. [Abstract] [Full Text] [PDF]