A Slow Transient Potassium Current Expressed in a Subset of Neurosecretory Neurons of the Hypothalamic Paraventricular Nucleus

Abstract

Type I putative magnocellular neurosecretory cells of the hypothalamic paraventricular nucleus (PVN) express a prominent transient outward rectification generated by an A-type potassium current. Described here is a slow transient outward current that alters cell excitability and firing frequency in a subset of type I PVN neurons (38%). Unlike most of the type I neurons (62%), the transient outward current in these cells was composed of two kinetically separable current components, a fast activating, fast inactivating component, resembling an A-type potassium current, and a slowly activating [10–90% rise time: 20.4 ± 12.8 (SE) ms], slowly inactivating component (time constant of inactivation: τ = 239.0 ± 66.1 ms). The voltage dependence of activation and inactivation and the sensitivity to block by 4-aminopyridine (5 mM) and tetraethylammonium chloride (10 mM) of the fast and slow components were similar. Compared to the other type I neurons, the neurons that expressed the slow transient outward current were less excitable when hyperpolarized, requiring larger current injections to elicit an action potential (58.5 ± 13.2 vs. 15.4 ± 2.4 pA; 250-ms duration; P < 0.01), displaying a longer delay to the first spike (184.9 ± 15.7 vs. 89.7 ± 8.8 ms with 250- to 1,000-ms, 50-pA current pulses; P < 0.01), and firing at a lower frequency (18.7 ± 4.6 vs. 37.0 ± 5.5 Hz with 100-pA current injections; P < 0.05). These data suggest that a distinct subset of type I PVN neurons express a novel slow transient outward current that leads to a lower excitability. Based on double labeling following retrograde transport of systemically administered fluoro-gold and intracellular injection of biocytin, these cells are neurosecretory and are similar morphologically to magnocellular neurosecretory cells, although it remains to be determined whether they are magnocellular neurons.