Nitric oxide increases the activity of the apical 70-pS K+ channel in TAL of rat kidney.
We have previously shown that nitric oxide (NO) mediates the stimulatory effect of angiotensin II on the apical 70-pS K+ channel in the thick ascending limb (TAL) of Henle's loop of the rat kidney (12). In the present study, we used the patch-clamp technique to examine the effects of NO on the 70-pS K+ channel. Addition of 10 microM S-nitroso-N-acetylpenicillamine (SNAP), a NO donor, increased the channel activity in cell-attached patches. In contrast, application of 100 microM N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), reduced the channel activity by 75 +/- 7%. The effect of L-NAME was the result of inhibiting NOS, since D-NAME, which does not block NOS activity, had no effect on the channel activity. In addition, the effect of L-NAME was abolished in the presence of 1 mM L-arginine or by addition of 10 microM SNAP, further supporting the role of NO. Finally, the L-NAME-induced inhibition was also reversed by adding 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP). That the effect of NO is mediated by the cGMP-dependent pathway is also suggested by experiments in which inhibition of guanylate cyclase abolished the effect of SNAP. Finally, 10 microM SNAP significantly increased cGMP concentration of the medullary TAL from 12.4 fM/microgram protein to 38.9 fM/microgram protein, as measured with ELISA. We conclude that NO is involved in regulating the activity of the apical 70-pS K+ channel in the TAL of the rat kidney.
Lu
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M
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Wang
X
X
Wang
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W
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008138:Loop of Henle / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D015221:Potassium Channels; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D010396:Penicillamine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester