Elektrophysiologie / Electrophysiology
(Leitung: Prof. Dr. Wolf-Michael Weber)
Role of sodium on protein expression (Project 1)
We used Xenopus laevis oocytes for the coexpression of human CFTR and ENaC derived from rat distal colon. We found no inhibition of ENaC by CFTR neither
with stimulated nor unstimulated CFTR. However, coexpression of ENaC with CFTR accelerated CFTR expression. Moreover, coexpression resulted in a tenfold
stimulation of cAMP-induced CFTR current (ICFTR) and conductance (GCFTR). This stimulation is dependent on active ENaC since amiloride,
a potent blocker of ENaC prevented CFTR up-regulation. CFTR up-regulation occurs via a sodium-dependent mechanism since removing of external sodium resulted in
the inhibition of ICFTR and GCFTR. Measuring the intracellular sodium concentration we found that elevation of intracellular sodium by ~ 1mM (i.e. from 5.5 to 6.6 mM) doubled CFTR and ENaC up-regulation. Yet, up-regulation of CFTR is independent of the presence of ENaC because elevating intracellular
sodium via the endogenous sodium/glucose-cotransporter also stimulated CFTR and ENaC currents threefold. ENaC expression and/or activity itself is strongly influenced
by the intracellular sodium concentration in the same way as for CFTR. Furthermore, reducing intracellular sodium inhibited the expression of ENaC, while increasing it
also stimulated expression of the human sodium/glucose cotransporter SGLT1. From these data we conclude that, at least in Xenopus laevis oocytes, heterologous
expression of transport proteins is a sodium-dependent process. Increased expression and/or activity of the transport proteins investigated so far, i.e. ENaC, CFTR and
SGLT1, is strongly dependent on the intracellular sodium concentration.More
information: http://www.uni-muenster.de/Biologie.Zoophysiologie/electrophys/ElectroHome.htm
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