title: Role of K(+) channels in frequency regulation of spontaneous action potentials in rat pituitary GH(3) cells.
abstract: The frequency of spontaneous action potentials (SAP) is important in the regulation of hormone secretion. The decrease in K(+) conductance is known as a primary mechanism for increasing SAP frequency. To investigate the nature of K(+) channels that contribute to the frequency regulation of the SAP in rat clonal pituitary GH(3) cells, the effect of various K(+) channel blockers on the SAP and membrane currents were recorded using the patch-clamp technique. A classical inward rectifying K(+) channel blocker, Cs(+) (5 mM), caused an increase in firing frequency and depolarization in after-hyperpolarization (AHP) voltage. An ETHER-A-GO-GO(ERG) type K(+) channel blocker, E-4031 (5 microM), caused no significant effect on the SAP. Tetraethylammonium (TEA, 10 mM) decreased firing frequency and increased the duration of SAP. These effects were not changed by the presence of high concentration of Ca(2+) buffer (10 mM EGTA or BAPTA) in pipette solutions. In voltage-clamp experiments, Cs(+) and E-4031 did not affect outwardly rectifying K(+) currents, but significantly inhibited inwardly rectifying K(+) currents recorded in isotonic K(+) solution. However, the kinetics of Cs(+)-sensitive current and E-4031-sensitive current were distinctive: the time to peak was more immediate and the decay rate was slower in Cs(+)-sensitive current than in E-4031-sensitive current. These results imply that Cs(+) and E-4031 inhibit the distinct components of inwardly rectifying K(+) currents, and that the contribution of the Cs(+)-sensitive current can be immediate on repolarization and can last more effectively over pacemaking potential range than E-4031-sensitive current.
authors.affiliation: Department of Physiology, Seoul National University, College of Medicine, Seoul, Korea.
authors.forename: Suk-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun Hae
authors.initials: EH
authors.lastname: Lee
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Ryu
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Baek
authors.forename: Wonil
authors.initials: W
authors.lastname: Lim
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002586:Cesium / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D016257:Fura-2 / Q000031:analogs & derivatives* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D002614:Chelating Agents; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; C049925:fura-2-am; C063968:E 4031; D002586:Cesium; D004533:Egtazic Acid; D019789:Tetraethylammonium; D002118:Calcium; D016257:Fura-2