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001-es BibID:BIBFORM032937
035-os BibID:PMID:17158651
Első szerző:Schroder, Elizabeth
Cím:Chronic verapamil treatment remodels ICa,L in mouse ventricle / Elizabeth Schroder, Janos Magyar, Don Burgess, Douglas Andres, Jonathan Satin
Dátum:2007
ISSN:0363-6135
Megjegyzések:In this study we tested the hypothesis that ventricular homeostasis of L-type Ca(2+) current (I(Ca,L)) minimally involves regulation of the main pore-forming alpha-subunit (Ca(V)1.2) and auxiliary proteins that serve as positive or negative regulators of I(Ca,L). We treated animals for 24 h with verapamil (Ver, 3.6 mg.kg(-1).day(-1)), isoproterenol (Iso, 30 mg.kg(-1).day(-1)), or Iso + Ver via osmotic minipumps. To test for alterations of Ca(2+) channel complex components we performed real-time PCR and Western blot analysis on ventricle. In addition, cardiac myocytes (CMs) were dispersed and current was recorded in the whole cell configuration to evaluate I(Ca,L). Surprisingly, 24- to 48-h Ver increased Ca(V)1.2 mRNA and protein and I(Ca,L) current (Ver 11 +/- 1pA/pF vs. control 7 +/- 0.5pA/pF; P < 0.01). I(Ca,L) from CMs in Ver mice showed no change in whole cell capacitance. To examine the in vivo effects of a physiologically relevant Ca(2+) channel agonist, we treated mice with Iso. Twenty-four-hour Iso infusion increased heart rate; Ca(V)1.2- and Ca(V)beta(2) mRNA levels were constant, but the Ca(2+) channel subunit mRNA Rem was increased twofold. Cells isolated from 24-h Iso hearts showed no change in basal I(Ca,L) density and diminished responsiveness to acute 1 muM Iso. To further examine the homeostatic regulation of the Ca(2+) channel, we treated animals for 24 h with Iso + Ver. The influence of Iso + Ver was similar that of to Iso alone on Ca(2+) channel mRNAs and I(Ca,L), with the exception that it prevented the increase in Rem seen with Iso treatment. Long-term Ca(2+) channel blockade induces an increase of Ca(V)1.2 mRNA and protein and significantly increases I(Ca,L).
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:American Journal of Physiology-Heart And Circulatory Physiology 292 : 4 (2007), p. H1906-H1916. -
További szerzők:Magyar János (1961-) (élettanász) Burgess, Don E. Andres, Douglas Satin, Jonathan
Internet cím:DOI
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