Disruption of microtubules in cultured neonatal rat cardiomyocytes during rapid contractions: protective effects of beta-adrenoceptor antagonist.
Tachycardia may play a key role in the progression of heart failure probably through Ca2+ overload. In the present study, to test whether microtubules, Ca(2+)-sensitive cytoskeletons, are disrupted by rapid contractions and whether the beta-adrenoceptor antagonist, propranolol could attenuate the disruption of microtubules, cultured neonatal rat cardiomyocytes with various contraction rates were studied. The microtubules were stained by immunohistochemical technique and the extent of microtubule disruption was quantified by disruption scores (grade 0-intact; grade 3-severe disruption). In 97% of the non-contracting cells, intact microtubules (grade 0) were observed, whereas in the cells that contract at the rate of 100-120/min, intact microtubules were observed only in 25% of the cells. The disruption scores were significantly correlated with contraction rates of the cells. Treatment with propranolol (10(-6)M) decreased the extent of microtubule disruption associated with a decrease in the contraction rate. However, this treatment did not alter the relationship between the contraction rate and the disruption score of microtubules. These results indicate that rapid contractions may induce disruption of microtubules which can be attenuated by beta-blocker mainly by its negative chronotropic effect. This may be one of the underlying mechanisms of the long-term effect of beta-blockers for chronic heart failure.
Hori
M
M
First Department of Medicine, Osaka University School of Medicine, Japan.
Sato
H
H
Iwai
K
K
Takashima
S
S
Sato
H
H
Inoue
M
M
Kitabatake
A
A
Kamada
T
T
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D007150:Immunohistochemistry; D008870:Microtubules / Q000187:drug effects / Q000473:pathology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011433:Propranolol