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Titolo:
cAMP modulates the excitability of immortalized hypothalamic (GT1) neuronsvia a cyclic nucleotide-gated channel
Autore:
Charles, A; Weiner, R; Costantin, J;
Indirizzi:
Univ Calif Los Angeles, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif San Francisco, Sch Med, Dept Obstet & Gynecol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 6, volume: 15, anno: 2001,
pagine: 997 - 1009
SICI:
0888-8809(200106)15:6<997:CMTEOI>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
GONADOTROPIN-RELEASING-HORMONE; INTERCELLULAR CALCIUM WAVES; OLFACTORY RECEPTOR NEURONS; GMP-ACTIVATED CHANNEL; ROD OUTER SEGMENT; L-CIS-DILTIAZEM; LUTEINIZING-HORMONE; PULSATILE RELEASE; CELL-LINES; RHESUS-MONKEY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Charles, A Univ Calif Los Angeles, Dept Neurol, Sch Med, 710 Westwood Plaza, Los Angeles, CA 90095 USA Univ Calif Los Angeles 710 Westwood Plaza Los Angeles CA USA 90095
Citazione:
A. Charles et al., "cAMP modulates the excitability of immortalized hypothalamic (GT1) neuronsvia a cyclic nucleotide-gated channel", MOL ENDOCR, 15(6), 2001, pp. 997-1009

Abstract

GT1 cells are immortalized hypothalamic neurons that show spontaneous bursts of action potentials and oscillations in intracellular calcium concentration [Ca2+](i), as well as pulsatile release of GnRH. We investigated the role of cyclic nucleotide gated (CNG) channels in the activity of GT1 neurons using patch clamp and calcium imaging techniques. Excised patches from GT1 cells revealed single channels and macroscopic currents that were activated by either cAMP or cGMP. CNG channels from GT1 cells showed rapid transitions from open to closed states typical of heteromeric CNG channels, were selective for cations, and had an estimated single channel conductance of 60picosiemens (pS). Ca2+ inhibited the conductance of macroscopic currents and caused rectification of currents at increasingly positive and negative potentials. The membrane permeant cAMP analog Sp-cAMP-monophosphorothioate (Sp-cAMPS) increased the frequency of spontaneous Ca2+ oscillations in GT1 cells, whereas the Rp-cAMPS isomer had only a slight stimulatory effect on Ca2+ signaling. Forskolin, norepinephrine, and dopamine, all of which stimulate cAMP production in GT1 cells, each increased the frequency of Ca2+ oscillations. The effects of Sp-cAMPS or NE on Ca2+ signaling did not appear tobe mediated by protein kinase A, since treatment with either H9 or Rp-cAMPS did not inhibit the response. The CNG channel inhibitor L-cis-diltiazem inhibited cAMP-activated channels in GT1 cells. Both L-cis-diltiazem and elevated extracellular Ca2+ reversibly inhibited the stimulatory effects of cAMP-generating ligands or Sp-cAMP on Ca2+ oscillations. These results indicate that CNG channels play a primary role in mediating the effects of cAMP on excitability in GT1 cells, and thereby may be important in the modulationof GnRH release.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 07:39:16