title: The role of the inwardly rectifying K+ current in resting potential and thyrotropin-releasing-hormone-induced changes in cell excitability of GH3 rat anterior pituitary cells.
abstract: Exposure of GH3 rat anterior pituitary cells to cholera toxin for 2-4 h significantly increased the thyrotropin-releasing-hormone(TRH)-induced inhibition of the inwardly rectifying K+ current studied in patch-perforated voltage-clamped cells. On the other hand, the current reduction became almost totally irreversible after washout of the neuropeptide. Comparison of the effects elicited by the toxin with those of 8-(4-chlorophenylthio)-cAMP or forskolin plus isobutylmethylxanthine indicated that, although the irreversibility may be due, at least in part, to elevations of cAMP levels, the enhancement of the TRH-induced inhibition of the current is not mediated by the cyclic nucleotide. Only reductions on the inwardly rectifying K+ current, but not those elicited by TRH on voltage-dependent Ca2+ currents, were increased by the treatment with cholera toxin. In current-clamped cells showing similar rates of firing, the second phase of enhanced action-potential frequency induced by TRH was also significantly potentiated by cholera toxin. Measurements of [Ca2+]i oscillations associated with electrical activity, using video imaging with fura-2-loaded cells, demonstrated that cholera toxin treatment causes a clear reduction of spontaneous [Ca2+]i oscillations. However, this did not prevent the stimulatory effect of TRH on oscillations due to the action potentials. In cholera-toxin-treated cells, the steady-state, voltage dependence of inactivation of the inward rectifier was shifted by nearly 20 mV to more negative values. These data suggest that the inwardly rectifying K+ current plays an important role in maintenance of the resting K+ conductance in GH3 cells. Furthermore, the TRH-induced reductions on this current may be an important factor contributing to the increased cell excitability promoted by the neuropeptide.
authors.affiliation: Departamento de Biología Funcional Area de Bioquímica, Facultad de Medicina, Universidad de Oviedo, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Barros
authors.forename: C
authors.initials: C
authors.lastname: Villalobos
authors.forename: J
authors.initials: J
authors.lastname: García-Sancho
authors.forename: D
authors.initials: D
authors.lastname: del Camino
authors.forename: P
authors.initials: P
authors.lastname: de la Peña
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D015221:Potassium Channels; D005576:Colforsin; D013973:Thyrotropin-Releasing Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D015056:1-Methyl-3-isobutylxanthine