Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of membrane-bound protein serine/threonine phosphatases (PP) in modulating the renal ATP-sensitive K+ (KATP) channel was examined using the patch-clamp technique in principal cells of rat cortical collecting duct. In the absence of ATP, channel activity rapidly (11.2 s) declines (channel "rundown") upon excision of the membrane patches into control bath solutions (1 mM Mg2+, Ca2+ free). Both orthovanadate (5 mM), a broad-spectrum inhibitor of phosphatases except for Ca(2+)-dependent PP (PP-2B), and okadaic acid (OA, 1 microM), a potent inhibitor of PP types 1 and 2A (PP-1 and PP-2A), significantly slowed channel rundown. Removal of Mg2+ from the bath also slowed the rundown process. Incubation of cells with OA in the absence of Mg2+ or with orthovanadate in ATP-free solution maintained channel activity at levels of approximately 70% of control values for 3 min after membrane excision. In contrast, Ca2+ (0.1 mM) and calmodulin (1 microM) in the presence of 1 mM Mg2+, a condition in which PP-2B is stimulated, had no significant effect on the channel activity that persisted in the presence of OA and orthovanadate. Application of exogenous PP-2A (1 U/ml) to the cytosolic side of membrane in inside-out patches significantly inhibited channel activity to 35.0% of control, but the inhibitory-effects of PP-1 (1 U/ml) and PP-2B (20 micrograms/ml) were minor. These results suggest that rundown of the renal KATP channel after membrane excision results mainly from dephosphorylation of the channel or an associated protein by membrane-bound phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of ATP-sensitive K+ channel by membrane-bound protein phosphatases in rat principal tubule cell. 757 84

The basolateral membrane of the rat cortical collecting duct (CCD) principal cell is K+ conductive. Recently, two different K+ channels have been described, namely a small- and an intermediate-conductance K+ channel (s-K+ and i-K+) which most likely are responsible for the macroscopic K+ conductance. K+ channel activity was investigated at the single-channel level using the patch-clamp technique. Patch-clamp recordings were obtained from enzymatically isolated CCD segments and freshly isolated CCD cells using conventional cell-free, cell-attached, cell-attached-nystatin and slow-whole-cell methods. Both K+ channels showed rundown behaviour after excision. In an excised inside-out oriented membrane, K+ channels could be activated by simultaneous addition of 0.1 mmol/l (cyclic guanosine monophosphate (cGMP) and 0.1 mmol/l MgATP to the bath. The i-K+ was activated in 13 out of 45, the s-K+ in 15 out of 45, cases. No activation of either channel was observed with cGMP alone (0.1 mmol/l), MgATP alone (0.1 mmol/l), cGMP and guanosine triphosphate (GTP) (0.1 mmol/l each) or cyclic adenosine monophosphate (cAMP) and MgATP (0.1 mmol/l each) n = 15, 11, 7, 8, respectively). The activated s-K+ could be blocked by KT 5823 (n = 8), a specific inhibitor of a cGMP-dependent protein kinase (PKG). An inhibition of the activated i-K+ was seen in seven cases. The membrane potential hyperpolarized significantly after application of dibutyryl-cGMP (0.1 mmol/l, n = 6) or nitroprusside (10 mumol/l, n = 5), which is known to liberate NO and thus increase the intracellular cGMP level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:K+ channels in the basolateral membrane of rat cortical collecting duct are regulated by a cGMP-dependent protein kinase. 776 Dec 58