Cited 0 times in Scipus Cited Count

Subunit composition is a major determinant in high affinity binding of a Ca2+ channel blocker.

DC Field Value Language
dc.contributor.authorSuh-Kim, H-
dc.contributor.authorWei, X-
dc.contributor.authorBirnbaumer, L-
dc.date.accessioned2011-08-18T04:35:25Z-
dc.date.available2011-08-18T04:35:25Z-
dc.date.issued1996-
dc.identifier.issn0026-895X-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/3799-
dc.description.abstractSkeletal muscle L-type channels are the pharmacological receptors for Ca2+ channel antagonists, including dihydropyridines (DHPs). High affinity DHP binding to these channels in skeletal muscle membranes has been reported to be independent of Ca2+ addition and to become dependent on Ca2+ after solubilization. The channel is a multimeric complex composed of alpha 1, beta, gamma, and alpha 2 delta, of which alpha 1 is the pore-forming and DHP-binding component. In this study we coexpressed non-alpha 1 components with alpha 1 in L and COS cells and investigated their roles in the regulation of high affinity DHP binding by Mg2+ and Ca2+. No DHP binding to membranes of cells expressing alpha 1 beta alone was detected in the absence of Ca2+ or Mg2+. Addition of Mg2+ revealed the presence of (+)-PN200-110 (DHP) binding sites with a Kd of 1 nM. This affinity was 4-fold lower than that of skeletal muscle membrane binding sites (Kd = 0.25 nM). Addition of Ca2+ increased the affinity for DHP in membranes from alpha 1 beta-expressing cells to that seen in skeletal muscle membranes (Kd = 0.2-0.3 nM; EC50 of 0.2 microM). Ca2+ did not affect DHP binding to skeletal muscle membranes. Coexpression of all of the subunits completely recapitulated the high affinity DHP binding seen with skeletal muscle membranes in the absence of Ca2+ and Mg2+ (Kd = 0.15 nM). This affinity was unaffected by addition of Ca2+ or Mg2+. Coexpression of alpha 1 beta with either alpha 2 delta or gamma alone resulted in DHP binding intermediate between levels seen with alpha 1 beta and alpha 1 beta alpha 2 delta gamma. Thus, this study demonstrates that alpha 2 delta and gamma are essential for full reconstitution of the DHP binding characteristics of the skeletal muscle L-type Ca2+ channel/DHP receptor.-
dc.language.isoen-
dc.subject.MESHAniline Compounds-
dc.subject.MESHAnimals-
dc.subject.MESHCOS Cells-
dc.subject.MESHCalcium-
dc.subject.MESHCalcium Channel Blockers-
dc.subject.MESHCalcium Channels-
dc.subject.MESHCalcium Channels, L-Type-
dc.subject.MESHCations, Divalent-
dc.subject.MESHDihydropyridines-
dc.subject.MESHIsradipine-
dc.subject.MESHKinetics-
dc.subject.MESHMacromolecular Substances-
dc.subject.MESHMuscle, Skeletal-
dc.subject.MESHStimulation, Chemical-
dc.subject.MESHTransfection-
dc.titleSubunit composition is a major determinant in high affinity binding of a Ca2+ channel blocker.-
dc.typeArticle-
dc.identifier.pmid8913365-
dc.identifier.urlhttp://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8913365-
dc.contributor.affiliatedAuthor서, 해영-
dc.type.localJournal Papers-
dc.citation.titleMolecular pharmacology-
dc.citation.volume50-
dc.citation.number5-
dc.citation.date1996-
dc.citation.startPage1330-
dc.citation.endPage1337-
dc.identifier.bibliographicCitationMolecular pharmacology, 50(5). : 1330-1337, 1996-
dc.identifier.eissn1521-0111-
dc.relation.journalidJ00026895X-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Files in This Item:
There are no files associated with this item.

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse