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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-1-22
pubmed:abstractText
Previously, we have shown that murine HCN2 channels over-expressed in newborn and adult cardiac myocytes produce currents with different biophysical characteristics. To investigate the role of tyrosine kinase modulation in these age-dependent differences, we employed the broad spectrum tyrosine kinase inhibitor erbstatin. Our results demonstrated distinct and separable effects of erbstatin on channel gating and current amplitude and a marked age dependence to these effects. In newborn myocytes, erbstatin decreased current amplitude, shifted the activation relation negative, and slowed activation kinetics. The effect on activation voltage but not that on amplitude was absent when expressing a cAMP-insensitive mutant (HCN2R/E), while a C-terminal truncated form of HCN2 (HCN2DeltaCx) exhibited only the voltage dependent but not the amplitude effect of erbstatin. Thus, the action of erbstatin on the activation relation and current amplitude are distinct and separable in newborn myocytes, and the effect on activation voltage depends on the cAMP status of HCN2 channels. In contrast to newborn myocytes, erbstatin had no effect on HCN2 under control conditions in adult myocytes but induced a negative shift with no change in amplitude when saturated cAMP was added to the pipette solution. We conclude that erbstatin's effects on HCN2 current magnitude and voltage dependence are distinct and separable, and there are fundamental developmental differences in the heart that affect channel function and its modulation by the tyrosine kinase inhibitor erbstatin.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-10356287, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-10400919, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-10484414, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-10545140, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-10578143, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-10631290, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-11181013, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-11248683, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-11331358, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-11440985, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-12194012, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-12411393, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-12475982, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-14634823, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-15136567, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-15265006, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-15292205, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-15292247, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-15364609, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-15564593, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-16079136, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-16273123, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-16395601, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-16680072, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-17074978, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-17178405, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-17977941, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-1804968, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-18268365, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-2023118, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-2242040, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-2447874, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-6603410, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-8013266, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-8383515, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-8385773, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-9000433, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-9161982, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-9214688, http://linkedlifedata.com/resource/pubmed/commentcorrection/18696104-9242713
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0031-6768
pubmed:author
pubmed:issnType
Print
pubmed:volume
457
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
821-30
pubmed:dateRevised
2011-3-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Age-dependent differences in the inhibition of HCN2 current in rat ventricular myocytes by the tyrosine kinase inhibitor erbstatin.
pubmed:affiliation
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
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