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http://purl.uniprot.org/citations/18434521http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18434521http://www.w3.org/2000/01/rdf-schema#comment"Kisspeptin and its cognate receptor, GPR54, are critical for reproductive development and for the regulation of gonadotropin-releasing hormone (GnRH) secretion. Although kisspeptin has been found to depolarize GnRH neurons, the underlying ionic mechanism has not been elucidated. Presently, we found that kisspeptin depolarized GnRH neurons in a concentration-dependent manner with a maximum depolarization of 22.6 +/- 0.6 mV and EC(50) of 2.8 +/-0.2 nM. Under voltage-clamp conditions, kisspeptin induced an inward current of 18.2 +/-1.6 pA (V(hold) = -60 mV) that reversed near -115 mV in GnRH neurons. The more negative reversal potential than E(K)(+) (-90 mV) was caused by the concurrent inhibition of barium-sensitive, inwardly rectifying (Kir) potassium channels and activation of sodium-dependent, nonselective cationic channels (NSCCs). Indeed, reducing extracellular Na(+) (to 5 mM) essentially eliminated the kisspeptin-induced inward current. The current-voltage relationships of the kisspeptin-activated NSCC currents exhibited double rectification with negative slope conductance below -40 mV in the majority of the cells. Pharmacological examination showed that the kisspeptin-induced inward currents were blocked by TRPC (canonical transient receptor potential) channel blockers 2-APB (2-aminoethyl diphenylborinate), flufenamic acid, SKF96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), and Cd(2+), but not by lanthanum (100 microM). Furthermore, single-cell reverse transcription-PCR analysis revealed that TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7 subunits were expressed in GnRH neurons. Therefore, it appears that kisspeptin depolarizes GnRH neurons through activating TRPC-like channels and, to a lesser extent, inhibition of Kir channels. These actions of kisspeptin contribute to the pronounced excitation of GnRH neurons that is critical for mammalian reproduction."xsd:string
http://purl.uniprot.org/citations/18434521http://purl.org/dc/terms/identifier"doi:10.1523/jneurosci.5352-07.2008"xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/author"Zhang C."xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/author"Ronnekleiv O.K."xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/author"Kelly M.J."xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/author"Roepke T.A."xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/name"J Neurosci"xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/pages"4423-4434"xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/title"Kisspeptin depolarizes gonadotropin-releasing hormone neurons through activation of TRPC-like cationic channels."xsd:string
http://purl.uniprot.org/citations/18434521http://purl.uniprot.org/core/volume"28"xsd:string
http://purl.uniprot.org/citations/18434521http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18434521
http://purl.uniprot.org/citations/18434521http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18434521
http://purl.uniprot.org/uniprot/#_Q15726-mappedCitation-18434521http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18434521
http://purl.uniprot.org/uniprot/Q15726http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18434521