Cecilia Canessa, MD

In
our laboratory we examine the structure, function and regulation of two
types of sodium channels: the Epithelial Na + Channel (ENaC) and Acid
Sensing Ion Channels (ASIC). These proteins are structurally related
but serve very different functions. ENaC is expressed in the apical
side of epithelial cells involved in sodium absorption such as in
kidney, lung and colon. Mutations in the human ENaC genes produce
disorders of whole-body sodium balance and are characterized by
hypertension or sodium wasting. Our current work centers on mechanisms
that regulate activity, expression and traffic of ENaC in epithelial
cells specifically, on the role of a kinase known as serum-and
glucocorticoid-induced kinase or Sgk1.

The
ASICs are expressed in neurons of the central and peripheral nervous
systems. External protons gate ASIC but other stimuli are likely to be
more important physiological agonists. These channels have been
implicated in many functions including nociception, mechanoperception
and modulation of synaptic transmission. Our work centers in the
elucidation of the biophysical properties and gating of ASICs from many
vertebrate species.


We
use a broad range of experimental approaches and techniques that
include electrophysiology (patch-clamp, two-electrode voltage clamp,
short-circuit current), cloning of channels from evolutionary distant
species, modifications of channels and their expression in oocytes,
cell lines and in mice either trangenics or knockins.