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A cation channel in the thick ascending limb of Henle's loop of the mouse kidney: inhibition by adenine nucleotides.
Author(s) -
Paulais M,
Teulon J
Publication year - 1989
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1989.sp017656
Subject(s) - chemistry , loop of henle , nucleotide , biophysics , purine , adenine nucleotide , adenosine , membrane potential , biochemistry , nephron , enzyme , biology , renal function , gene
1. Patch‐clamp single‐channel current recordings were used to study the inhibition of Ca2+‐activated non‐selective cation channels by internal nucleotides in patches excised from basolateral membranes of the thick ascending limb of Henle's loop of the mouse kidney. 2. The application of ATP, ADP or AMP to the cytoplasmic face of excised inside‐out membrane patches reduced the open‐state probability of the channels (Po) in a dose‐dependent way without effect upon the unitary current amplitude. Dose‐response curves gave half‐maximal inhibitory concentrations of 20, 21 and 2.5 microM for ATP, ADP and AMP, respectively, while the Hill coefficient was close to one in all three cases. 3. Cyclic AMP partially inhibited channel activity (Po = 35 +/‐ 17% of control) only at high, unphysiological concentrations (10(‐3) M) while adenosine (10(‐3) M) had very little effect (Po = 83 +/‐ 7% of control). 4. Replacement of adenine with other purines (guanine, hypoxanthine) or pyrimidine (uridine) bases very largely reduced inhibitory activity. Cyclic GMP had no effect. 5. Non‐hydrolysable analogues of ATP, AMP‐PNP (10(‐3) M) and ATP‐gamma‐S (5 x 10(‐4) M), were effective inhibitors of the channel (Po = 24 +/‐ 7 and 9 +/‐ 4% of control, respectively.