The broad, long-term objectives and specific aims of the proposed research are the elucidation of salt and water transport by the kidney. It is planned to study the role of cell calcium ([cA2+]I) and protein kinase C (PKC)-mediated regulation of the amilordie- sensitive, small conductance Na channel. This channel is under the control of aldosterone and vasopressin and plays a critical role in the maintenance of salt and water balance in the body. More specifically, in rat renal cortical collecting tubules (CCTs), the effect of EGF will be assessed.- To test whether stimulation by cAMP masks the inhibitory action of high [Ca2+]I on Na channel activity the effect of ionomycin on channel activity will be examined in cAMP-pretreated CCTs. Furthermore, the identity of the specific isoforms of PKC in principal cells of the CCT and the degree to which they depend on changes in [Ca2+]I for activation and translocation will be determined by immunofluorescence imaging of antibodies specific to the isoforms.- using the whole cell patch clamp approach we will study the effect of specific inhibitors of PKC and Ca2+/CaM kinase II and of the addition of activated forms of these kinases on the Ca2+-mediated inhibition of the amiloride-sensitive Na current in principal cells. With the same approach, the effect of dephosphorylation by protein phosphatases will be explored.- Finally, the role of Na-self-inhibition of Na channels in the regulation of apical Na permeability in principal cells will be explored.
| Frindt, Gustavo; McNair, Tiffany; Dahlmann, Anke et al. (2002) Epithelial Na channels and short-term renal response to salt deprivation. Am J Physiol Renal Physiol 283:F717-26 |
| Weinstein, A M; Windhager, E E (2001) The paracellular shunt of proximal tubule. J Membr Biol 184:241-5 |
| Frindt, G; Masilamani, S; Knepper, M A et al. (2001) Activation of epithelial Na channels during short-term Na deprivation. Am J Physiol Renal Physiol 280:F112-8 |
| Mennitt, P A; Frindt, G; Silver, R B et al. (2000) Potassium restriction downregulates ROMK expression in rat kidney. Am J Physiol Renal Physiol 278:F916-24 |
| Silver, R B; Choe, H; Frindt, G (1998) Low-NaCl diet increases H-K-ATPase in intercalated cells from rat cortical collecting duct. Am J Physiol 275:F94-102 |
| Palmer, L G; Sackin, H; Frindt, G (1998) Regulation of Na+ channels by luminal Na+ in rat cortical collecting tubule. J Physiol 509 ( Pt 1):151-62 |
| Echevarria, M; Windhager, E E; Frindt, G (1996) Selectivity of the renal collecting duct water channel aquaporin-3. J Biol Chem 271:25079-82 |
| Mulders, S M; Olde Weghuis, D; van Boxtel, J A et al. (1996) Localization of the human gene for aquaporin 3 (AQP3) to chromosome 9, region p21-->p12, using fluorescent in situ hybridization. Cytogenet Cell Genet 72:303-5 |
| Frindt, G; Palmer, L G; Windhager, E E (1996) Feedback regulation of Na channels in rat CCT. IV. Mediation by activation of protein kinase C. Am J Physiol 270:F371-6 |
| Ecelbarger, C A; Terris, J; Frindt, G et al. (1995) Aquaporin-3 water channel localization and regulation in rat kidney. Am J Physiol 269:F663-72 |
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