University of California-Los Angeles
Endocrine cells have the intrinsic capacity for extensive spontaneous activity that is independent of stimulation by external factors. In both hypothalamic and pituitary cells, this activity is characterized by membrane potential oscillations, action potentials, and Ca2+ oscillations. We have used simultaneous video imaging of [Ca2+]i and patch clamp techniques to investigate the mechanisms of this spontaneous activity in the GH3 pituitary cell line and the GT1 hypothalamic cell line. In both cell types, the amplitude and frequency of Ca2+ oscillations, as well as baseline [Ca2+]i, can be specifically modulated by specific modulation of individual ion channels. In GH3 cells, L-type Ca2+ channels and inward rectifying K+ channels modulate the frequency of Ca2+ oscillations and prolactin release, whereas TEA-sensitive K+ channels modulate the amplitude of Ca2+ oscillations without altering prolactin release. These ion channels play similar roles in modulating of amplitude and frequency of spontaneous signaling in GT1 cells. In addition, GT1 cells show intercellular coupling via gap junctions that results in waves of increased [Ca2+]i that are communicated across fields of hundreds of cells. These intercellular Ca2+ waves are generated by propagated depolarization leading to bursts of action potentials that result in influx of Ca2+ through L-type channels. Cells that are coupled show distinctly different patterns of spontaneous activity, characterized by bursts of Ca2+ oscillations separated by intervals of inactivity. Gap junctional coupling may be an important mechanism not only for spatial and temporal coordination of cellular activity, but also for generation of rhythmic patterns of activity.