S. Kieferle et al., 2 HIGHLY HOMOLOGOUS MEMBERS OF THE CLC CHLORIDE CHANNEL FAMILY IN BOTH RAT AND HUMAN KIDNEY, Proceedings of the National Academy of Sciences of the United Statesof America, 91(15), 1994, pp. 6943-6947
We have cloned two closely related putative Cl- channels from both rat
kidney (designated rClC-K1 and rClC-K2) and human kidney (hClC-Ka and
hClC-Kb) by sequence homology to the ClC family of voltage-gated Cl-
channels. While rClC-K1 is nearly identical to ClC-K1, a channel recen
tly isolated by a similar strategy, rClC-K2 is 80% identical to rClC-K
1 and is encoded by a different gene. hClC-Ka and hClC-Kb show approxi
mate to 90% identity, while being approximate to 80% identical to the
rat proteins. All ClC-K gene products are expressed predominantly in t
he kidney. While rClC-K1 is expressed strongly in the cortical thick a
scending limb and the distal convoluted tubule, with minor expression
in the S3 segment of the proximal tubule and the cortical collecting t
ubule, rClC-K2 is expressed in all segments of the nephron examined, i
ncluding the glomerulus. Since they are related more closely to each o
ther than to the rat proteins, hClC-Ka and hClC-Kb cannot be regarded
as strict homologs of rClC-K1 or rClC-K2. After injection of ClC-K cRN
As into oocytes, corresponding proteins were made and glycosylated, th
ough no additional Cl- currents were detectable. Glycosylation occurs
between domains D8 and D9, leading to a revision of the transmembrane
topology model for ClC channels.