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)

We recently reported that M-1 mouse cortical collecting duct cells show nonselective cation (NSC) channel activity (Proc. Natl. Acad. Sci. USA 89:10262-10266, 1992). In this study, we further characterize the M-1 NSC channel using single-channel current recordings in excised inside-out patches. The M-1 NSC channel does not discriminate between Na+, K+, Rb+, Cs+, and Li+. It has a linear I-V relation with a conductance of 22.7 +/- 0.5 pS (n = 78) at room temperature. The Pcation/P(anion) ratio is about 60 and there is no measurable conductance for NMDG, Ca2+, Ba2+, and Mn2+. Cytoplasmic calcium activates the M-1 NSC channel at a threshold of 10(-6) M and depolarization increases channel activity (NPo). Cytoplasmic application of adenine nucleotides inhibits the M-1 NSC channel. At doses of 10(-4) M and 10(-3) M, ATP reduces NPo by 23% and 69%, respectively. Furthermore, since ADP (10(-3) M) reduces NPo by 93%, the inhibitory effect of adenine nucleotides is not dependent on the presence of a gamma-phosphoryl group and therefore does not involve protein phosphorylation. The channel is not significantly affected by 8-Br-cGMP (10(-4) M) or by cGMP-dependent protein kinase (10(-7) M) in the presence of 8-Br-cGMP (10(-5) M) and ATP (10(-4) M). The NSC channel is not sensitive to amiloride (10(-4) M cytoplasmic and/or extracellular) but flufenamic acid (10(-4) M) produces a voltage-dependent block, reducing NPo by 35% at depolarizing voltages and by 80% at hyperpolarizing voltages. We conclude that the NCS channel of M-1 mouse cortical collecting duct cells belongs to an emerging family of calcium-activated and nucleotide-sensitive nonselective cation channels. It does not contribute to amiloride-sensitive sodium absorption and is unlikely to be a major route for calcium entry. The channel is normally quiescent but may be activated under special physiological conditions, e.g., during volume regulation.
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PMID:A calcium-activated and nucleotide-sensitive nonselective cation channel in M-1 mouse cortical collecting duct cells. 756 35

We used the patch-clamp technique to study the effect of cGMP on the 18-pS K channel in the basolateral membrane of the rat cortical collecting duct. Addition of 100 microM 8-bromoguanosine 3', 5'-cyclic monophosphate (8-Br-cGMP) increased the activity of the 18-pS K channel, defined by NP(o), by 95%. In contrast, applying 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) has no effect on channel activity. The effect of 8-Br-cGMP was observed only in cell-attached but not in inside-out patches. Application of 1 microM KT-5823, an inhibitor of the cGMP-dependent protein kinase (PKG), not only reduced the channel activity, but also completely abolished the stimulatory effect of 8-Br-cGMP, suggesting that the 18-pS K channel is not a cGMP-gated K channel. Addition of H-89, an agent that also blocks the PKG, mimicked the effect of KT-5823. To examine the possibility that the effect of 8-Br-cGMP is the result of inhibiting cGMP-dependent phosphodiesterase (PDE) and, accordingly, increasing cAMP or cGMP levels, we explored the effect on the 18-pS K channel of IBMX, an agent that inhibits the PDE. The addition of 100 microM IBMX had no significant effect on channel activity in cell-attached patches. Moreover, in the presence of IBMX, 8-Br-cGMP increased the channel activity to the same extent as that observed in the absence of IBMX, suggesting that the effect of cGMP is not mediated by inhibiting the cGMP-dependent PDE. That the effect of cGMP is mediated by stimulating PKG was further indicated by experiments in which application of exogenous PKG restored the channel activity when it decreased after the excision of the patches. In contrast, adding exogenous cAMP-dependent protein kinase catalytic subunit failed to reactivate the run-down channels. We conclude that cGMP stimulates the 18-pS channel, and the effect of cGMP is mediated by PKG.
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PMID:The cGMP-dependent protein kinase stimulates the basolateral 18-pS K channel of the rat CCD. 1083 49