Remodeling excitation-contraction coupling of hypertrophied ventricular myocytes is dependent on T-type calcium channels expression

Biochem Biophys Res Commun. 2006 Jun 30;345(2):766-73. doi: 10.1016/j.bbrc.2006.04.146. Epub 2006 May 5.

Abstract

We utilized Wistar rats with monocrotaline (MCT)-induced right ventricular hypertrophy (RVH) in order to evaluate the T-type Ca2+ channel current (ICaT) for myocardial contraction. RT-PCR provides that mRNA for T-type Ca2+ channel alpha1-subunits in hypertrophied myocytes was significantly higher than those in control rats (alpha1G; 264+/-36%, alpha1H; 191+/-34%; P<0.05). By whole-cell patch-clamp study, ICaT was recorded only in hypertrophied myocytes but not in control myocytes. The application of 50 nmol/L nifedipine reduced the twitch tension of the right ventricles equally in the control and RVH rats. On the other hand, 0.5 micromol/L mibefradil, a T-type Ca2+ channel blocker, strongly inhibited the twitch tension of the RVH muscle (control 6.4+/-0.8% vs. RVH 20.0+/-2.3% at 5 Hz; P<0.01). In conclusion, our results indicate the functional expression of T-type Ca2+ channels in the hypertrophied heart and their contribution to the remodeling of excitation-contraction coupling in the cardiac myocyte.

MeSH terms

  • Animals
  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / metabolism*
  • Gene Expression
  • Heart / drug effects
  • Heart / physiology*
  • Hypertrophy, Right Ventricular / chemically induced
  • Monocrotaline / pharmacology
  • Myocardial Contraction / physiology*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology*
  • Nifedipine / pharmacology
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stimulation, Chemical

Substances

  • Calcium Channels, T-Type
  • Monocrotaline
  • Nifedipine