Modulation of Ca2+ signaling by K+ channels in a hypothalamic neuronal cell line (GT1-1)

The pulsatile release of gonadotropin releasing hormone (GnRH) is driven by the intrinsic activity of GnRH neurons, which is characterized by bursts o f action potentials correlated with oscillatory increases in intracellular Ca2+. The role of K+ channels in this spontaneous activity was studied by e xamining the effects of commonly used K+ channel blockers on K+ currents, s pontaneous action currents, and spontaneous Ca2+ signaling. Whole-cell reco rdings of voltage-gated outward K+ currents in GT1-1 neurons revealed at le ast two different components of the current. These included a rapidly activ ating transient component and a more slowly activating, sustained component . The transient component could be eliminated by a depolarizing prepulse or by bath application of 1.5 mM 4-aminopyridine (4-AP). The sustained compon ent was partially blocked by 2 mM tetraethylammonium (TEA). GT1-1 cells als o express inwardly rectifying K+ currents (I-K(IR)) that were activated by hyperpolarization in the presence of elevated extracellular K+. These curre nts were blocked by 100 muM Ba2+ and unaffected by 2 mM TEA or 1.5 mM 4-AP. TEA and Ba2+ had distinct effects on the pattern of action current bursts and the resulting Ca2+ oscillations. TEA increased action current burst dur ation and increased the amplitude of Ca2+ oscillations. Ba2+ caused an incr ease in the frequency of action current bursts and Ca2+ oscillations. These results indicate that specific subtypes of K+ channels in GT1-1 cells can have distinct roles in the amplitude modulation or frequency modulation of Ca2+ signaling. K+ current modulation of electrical activity and Ca2+ signa ling may be important in the generation of the patterns of cellular activit y responsible for the pulsatile release of GnRH.