17β-estradiol inhibits outward potassium currents recorded in rat parabrachial nucleus cells in vitro

Evidence is increasingly accumulating in support of a role for the steroid hormone 17β-estradiol to modify neuronal functions in the mammalian CNS, especially in autonomic centers. In addition to its well known slowly developing and long lasting actions (genomic), estrogen can also rapidly modulate cell signaling events by affecting membrane excitability (non-genomic). Little, however, is known regarding the mechanism(s) by which 17β-estradiol produces its rapid effects on neuronal membrane excitability. As potassium channels play a crucial role in cell excitability, we hypothesized that 17β-estradiol caused excitability by modulating potassium flux through the neuronal cell membrane. We tested this hypothesis by examining the effects of 17β-estradiol on outward potassium currents recorded in cells from the parabrachial nucleus of rats, in vitro. Bath application of 17β-estradiol (10-100μM) reversibly reduced voltage-activated outward potassium currents in a concentration-dependent manner. This effect was mimicked by BSA-17β-estradiol but not mimicked by 17α-estradiol and was significantly reduced by ICI 182,780, a selective estrogen receptor antagonist. The inhibitory effect of 17β-estradiol was dependent on extracellular potassium concentration, with more profound effects observed at lower concentrations. The 17β-estradiol-induced inhibition of the outward current was blocked by pretreatment with the potassium channel blockers tetraethylammonium and 4-aminopyridine. The time constants of deactivation of tail currents were decreased by 17β-estradiol over a range of test potentials (−140 to −80 mV). Finally, the inhibitory effect of 17β-estradiol on the outward potassium currents was blocked following pre-incubation of slices in lavendustin A, a tyrosine kinase inhibitor. Taken together, these results suggest that 17β-estradiol acts rapidly at an extracellular membrane receptor to reduce tetraethylammonium- and 4-aminopyridine-sensitive outward potassium currents by accelerating the closure of potassium channels. This may be the ionic basis of 17β-estradiol-induced enhancement of neuronal excitability.