Chronic verapamil treatment remodels ICa,L in mouse ventricle

8, 2006; doi:10.1152/ajpheart.00793.2006.—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 -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 kg1 day1), isoproterenol (Iso, 30 mg kg1 day1), or Iso Ver via osmotic minipumps. To test for alterations of Ca2 channel com-plex 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). ICa,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 wit