Chronic verapamil treatment remodels ICa,L in mouse ventricle

Elizabeth Schroder, Janos Magyar, Don Burgess, Douglas Andres, Jonathan Satin

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


In this study we tested the hypothesis that ventricular homeostasis of L-type Ca2+ current (ICa,L) minimally involves regulation of the main pore-forming α-subunit (CaV1.2) and auxiliary proteins that serve as positive or negative regulators of ICa,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 Ca2+ 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 ICa,L. Surprisingly, 24- to 48-h Ver increased CaV1.2 mRNA and protein and ICa,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 Ca2+ channel agonist, we treated mice with Iso. Twenty-four-hour Iso infusion increased heart rate; CaV1.2- and CaVβ2 mRNA levels were constant, but the Ca2+ channel subunit mRNA Rem was increased twofold. Cells isolated from 24-h Iso hearts showed no change in basal ICa,L density and diminished responsiveness to acute 1 μM Iso. To further examine the homeostatic regulation of the Ca2+ channel, we treated animals for 24 h with Iso + Ver. The influence of Iso + Ver was similar that of to Iso alone on Ca2+ channel mRNAs and ICa,L, with the exception that it prevented the increase in Rem seen with Iso treatment. Long-term Ca2+ channel blockade induces an increase of Ca V1.2 mRNA and protein and significantly increases ICa,L.

Original languageEnglish
Pages (from-to)H1906-H1916
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4
StatePublished - Apr 2007


  • Calcium channel blockade
  • Electrocardiogram
  • Electrophysiology
  • Ventricle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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