Remodeling excitation-contraction coupling of hypertrophied ventricular myocytes is dependent on T-type calcium channels expression.
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.
Takebayashi
Satoshi
S
Department of Cardiovascular Science, Oita University School of Medicine, Oita 879-5593, Japan.
Li
Yulong
Y
Kaku
Toshihiko
T
Inagaki
Shuichiro
S
Hashimoto
Yutaka
Y
Kimura
Kazuhiro
K
Miyamoto
Shinji
S
Hadama
Tetsuo
T
Ono
Katsushige
K
D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced; D016686:Monocrotaline / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical
D020747:Calcium Channels, T-Type; D016686:Monocrotaline; D009543:Nifedipine