The structure and function of serpins

From Frog Skin to Human Colon:
The mechanisms of epithelial crosstalk
16
We key nux in these cells is the abrqtion of sodium ions.
Sodim EIUI the cell through a sodium channel at the apical
membrane (the one facing the enema1 envimnmmt) and exits
at the baroiateral membrane (which facer body tirrues)
through a rodiumlpotarrium pump: the imported potassium
leak out thmugh a potassium channel ($te above). To replate
sdwm levl. the actiwtier oflhe sodium channel muR some.
haw be linked to those ofthe ion vansponen at the bardatatcr.
al membranc. A decade or rc'r work by Pmfmor han Harvey
and ioileaguer. fim in France but m m recently in Coh his
identified three mmponenu of lhir in~dcellulir imrnalk ryrtern:
pH, ATP 10 ADP ratio and calcium,
INTRACELLUIAR pH
We 6m edence that intracellular pH could be significant
sme in the 1980s. with the discovery that the sodium and .
poliiiium conductances dfmg Mn epithelia increased mth
increasing pH. Morewer, the efeN w e innaniamots and
occurred afierphyriologirally relevant Shi& in pH. Literpatch.
clamping rtudier revealed that individual potaiiium and sodium
cha~elr are directly modulated by pH. The $odiumlpotanium
pump. however. is relatively insemirive 10 intracellular pH.
Two a m ofthe ion transport rynem thus appear to be COY.
pled. via intracellular pH. How might this iwpling be linked to
the contml of ion tranipoTi1 Studies in fmg skin revealed that
in1racellulai pH is sensitive to m!ei of ion transort. We key
factor appearr 10 be a rodnrdpmton exchanger in the basola.
en1 membrane. whrh pumps pmtonr out ofthe cell and thus
increaser intraceiluIrpH. The exchangeri'doven by the rodium
gradient imii the membrane, IO any bdd.up of $odium
in the cell wII. thmugh ils eiTeitr on pH. inhiba funher $odium
17
inOvx lree abovel. In e kt 8 'ïeedback h W mmtes