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http://purl.uniprot.org/citations/15351778http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15351778http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15351778http://www.w3.org/2000/01/rdf-schema#comment"The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was heterologously expressed in mammalian cell lines (CV-1 and CHO) and its properties investigated using whole-cell patch-clamp recordings. Activation of this recombinant channel, by membrane hyperpolarization, generated a slowly activating, noninactivating inward current. The pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (I(h)), that is, blockade by Cs(+) (99% at 5 mm), ZD 7288 (98% at 100 microm) and zatebradine (92% at 10 microm). Inhibition of the hHCN1-mediated current by ZD 7288 was apparently independent of prior channel activation (i.e. non-use-dependent), whereas that induced by zatebradine was use-dependent. The VR1 receptor antagonist capsazepine inhibited hHCN1-mediated currents in a concentration-dependent (IC(50)=8 microm), reversible and apparently non-use-dependent manner. This inhibitory effect of capsazepine was voltage-independent and associated with a leftward shift in the hHCN1 activation curve as well as a dramatic slowing of the kinetics of current activation. Elevation of intracellular cAMP or extracellular K(+) significantly enhanced aspects of hHCN1 currents. However, these manipulations did not significantly affect the capsazepine-induced inhibition of hHCN1. The development of structural analogues of capsazepine may yield compounds that could selectively inhibit HCN channels and prove useful for the treatment of neurological disorders where a role for HCN channels has been described."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.org/dc/terms/identifier"doi:10.1038/sj.bjp.0705945"xsd:string
http://purl.uniprot.org/citations/15351778http://purl.org/dc/terms/identifier"doi:10.1038/sj.bjp.0705945"xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Hill K."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Hill K."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Gill C.H."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Gill C.H."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Yusaf S.P."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Yusaf S.P."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Owen D."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Owen D."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Powell A.J."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Powell A.J."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Murdock P.R."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Murdock P.R."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Bates S.A."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Bates S.A."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Strijbos P.J."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Strijbos P.J."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Benham C.D."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Benham C.D."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Cairns W."xsd:string
http://purl.uniprot.org/citations/15351778http://purl.uniprot.org/core/author"Cairns W."xsd:string