Teruyama R, Sakuraba M, Wilson LL, Wandrey NE, Armstrong WE. Epithelial Na ϩ sodium channels in magnocellular cells of the rat supraoptic and paraventricular nuclei. Am J Physiol Endocrinol Metab 302: E273-E285, 2012. First published November 1, 2011; doi:10.1152/ajpendo.00407.2011.-The epithelial Na ϩ channels (ENaCs) are present in kidney and contribute to Na ϩ and water homeostasis. All three ENaC subunits (␣, ␤, and ␥) were demonstrated in the cardiovascular regulatory centers of the rat brain, including the magnocellular neurons (MNCs) in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). However, the functional significance of ENaCs in vasopressin (VP) and oxytocin (OT) synthesizing MNCs is completely unknown. In this study, we show with immunocytochemical double-labeling that the ␣-ENaC is colocalized with either VP or OT in MNCs in the SON and PVN. In addition, parvocellular neurons in the dorsal, ventrolateral, and posterior subregions of the PVN (not immunoreactive to VP or OT) are also immunoreactive for ␣-ENaC. In contrast, immunoreactivity to ␤-and ␥-ENaC is colocalized with VP alone within the MNCs. Furthermore, immunoreactivity for a known target for ENaC expression, the mineralcorticoid receptor (MR), is colocalized with both VP and OT in MNCs. Using single-cell RT-PCR, we detected mRNA for all three ENaC subunits and MR in cDNA libraries derived from single MNCs. In whole cell voltage clamp recordings, application of the ENaC blocker benzamil reversibly reduced a steady-state inward current and decreased cell membrane conductance approximately twofold. Finally, benzamil caused membrane hyperpolarization in a majority of VP and about one-half of OT neurons in both spontaneously firing and quiet cells. These results strongly suggest the presence of functional ENaCs that may affect the firing patterns of MNCs, which ultimately control the secretion of VP and OT. aldodsterone; vasopressin; oxytocin THE NEUROHYPOPHYSIAL HORMONES vasopressin (VP) and oxytocin (OT) are synthesized in the magnocellular neurons (MNCs) located within the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus and released from the neurohypophysis into the general circulation in response to physiological demands. The secretion of VP increases in response to hyperosmolality, hypovolemia, and hypotension and produces antidiuretic and pressor effects (59). In addition to the well-known effects of OT during parturition and lactation, plasma OT also increases with hyperosmolality and hypernatremia (32) and induces natriuresis (13, 31).The non-voltage-dependent, amiloride-sensitive epithelial Na ϩ channels (ENaCs) are present in the apical membrane of epithelial cells in a variety of tissues, such as urinary bladder, renal collecting duct, distal colon, sweat and salivary glands, lung, and taste buds, and are known to mediate the transport of Na ϩ across epithelia (7, 21). Thus, together with the Na ϩ /K ϩ -ATPase present in the basal membrane of epithelial cells, ENaCs regulate transe...

A 59-year-old man presented with an unresectable bulky giant basal cell carcinoma on his upper back. A trial of chemotherapy did not help relieve his symptoms or reduce the tumor. He was referred for and received definitive radiation therapy via IMRT with dramatic regression. The patient had been unable to lie on his back for many years but currently can sleep comfortably on his back without pain, which has dramatically improved his quality of life.

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