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 muM), 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 Ca2+ 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. Copyright (C) 2003 S. Karger AG, Basel.