Cellular and molecular physiology of volume-sensitive anion
channels.
Strange, Kevin, Francesco Emma, and Paul S. Jackson.
Critical Care Research Laboratories, Departments of Medicine
(Nephrology) and Neurosurgery, Children's Hospital and Harvard
Medical School, Boston, MA 02115
APStracts 2:0289C, 1995.
Maintenance of a constant cell volume in the face of osmotic stress is
an evolutionarily ancient homeostatic processes. Over the last two
decades physiologists have gained an impressive understanding of the
'volume-sensitive' channels, cotransporters, exchangers, metabolic
pathways and genes that are responsible for modulating intracellular
solute content and cell volume. This review focuses on one part of
this story, the characteristics and osmoregulatory functions of
volume-sensitive anion channels. Three distinct types of swelling
-activated anion channels have been observed widely and described in
animal cells. These channels include 1) ClC-2, which is a member of
the ClC family of voltage-gated anion channels, 2) an outwardly
rectifying, intermediate conductance channel, and 3) a large
conductance or 'maxi' channel. ClC-2 was cloned originally from rat
brain and has provided our first view of the molecular workings of a
volume-sensitive transport pathway. Recent evidence suggests that the
'maxi' channel may also now be cloned. The outwardly rectifying anion
channel is not only a volume regulatory Cl- efflux pathway, but also
the major pathway for the swelling-induced loss of organic osmolytes
and probably various organic anions from the cell. Consequently, this
channel has been termed VSOAC for Volume-Sensitive Organic
osmolyte/Anion Channel. ICln, a protein cloned recently from dog
kidney cells appears to be either the VSOAC channel, a component of
the channel, or a regulator of VSOAC. In addition to these three
channels, several other less well-characterized anion channels have
been observed. This review will discuss the electrophysiological and
molecular biological characteristics, and regulation of these
channels. We will also discuss the possible roles different types of
anion channels might play in cell volume homeostasis.
Received 1 June 1995; accepted in final form 14 July 1995.
APS Manuscript Number C474-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.