Abstract
BackgroundThe hypothalamic paraventricular nucleus (PVN) is an important site in the regulation of the autonomic nervous system. Specifically, PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) play a regulatory role in the determination of the sympathetic outflow in the cardiovascular system. In the PVN-RVLM neurons, the estrogen receptor β is expressed. However, to date, the effects of estrogen on PVN-RVLM neurons have not been reported. The present study investigated estrogen-mediated modulation of two voltage-gated potassium channel (Kv) subunits, Kv4.2 and Kv4.3, that are expressed predominantly in PVN neurons and the functional current of Kv4.2 and Kv4.3, the transient outward potassium current (IA).ResultsSingle-cell real-time RT-PCR analysis showed that 17β-estradiol (E2) replacement (once daily for 4 days) selectively down-regulated Kv4.2 mRNA levels in the PVN-RVLM neurons of ovariectomized female rats. There was no change in Kv4.3 levels. Whole-cell patch-clamp recordings demonstrated that E2 also diminished IA densities. Interestingly, these effects were most apparent in the dorsal cap parvocellular subdivision of the PVN. E2 also shortened a delay in the excitation of the PVN-RVLM neurons.ConclusionsThese findings demonstrate that E2 exerts an inhibitory effect on the functions of IA, potentially by selectively down-regulating Kv4.2 but not Kv4.3 in PVN-RVLM neurons distributed in a specific parvocellular subdivision.
Highlights
The hypothalamic paraventricular nucleus (PVN) is an important site in the regulation of the autonomic nervous system
Retrograde labeling of PVN-rostral ventrolateral medulla (RVLM) neurons To identify the PVN-RVLM neurons for recording and single-cell real-time RT-PCR, fluorescent tracer was injected into the RVLM of OVX-rats
The PVN-RVLM neurons were located primarily in the three main PVN subdivisions: the dorsal cap (DC), the ventral parvocellular (PaV), and the posterior parvocellular (PaPo), which was consistent with the previous report [13]
Summary
The hypothalamic paraventricular nucleus (PVN) is an important site in the regulation of the autonomic nervous system. The presympathetic neurons project directly to the intermediolateral column in the spinal cord where the sympathetic preganglionic nuclei are concentrated or project indirectly via the rostral ventrolateral medulla (RVLM) to influence cardiovascular sympathetic outflows [2]. The distributional pattern of ER-β in the PVN is similar to that of the parvocellular cells projecting to the brain stem or spinal cord [11,12]. This similarity was confirmed by the observation that PVN-RVLM neurons identified by retrograde tracing expressed ER-β [13]. The effects of estrogen on this specific cell population have not been studied
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