Three widely documented mechanisms of chloride transport across plasma
membranes are anion-coupled antiport, sodium-coupled symport, and an
electrochemical coupling process. No direct genetic evidence has yet b
een provided for primary active chloride transport despite numerous re
ports of cellular Cl--stimulated adenosine triphosphate (ATP)ases coex
isting in the same tissue with uphill chloride transport that could no
t be accounted for by the three common chloride transport processes. C
l--stimulated ATPases are a common property of practically all biologi
cal cells, with the major location being of mitochondrial origin. It a
lso appears that plasma membranes are sites of Cl--stimulated ATPase a
ctivity. Recent studies of Cl--stimulated ATPase activity and chloride
transport in the same membrane system, including liposomes, suggest a
mediation by the ATPase in net movement of chloride up its electroche
mical gradient across plasma membranes. Further studies, especially fr
om a molecular biological perspective, are required to confirm a direc
t transport role to plasma membrane-localized Cl--stimulated ATPases.