Publication: Inhibition of connexin43 dephosphorylation
is involved in protective effects of diltiazem
on cardiac function during hypoxic injury
Authors
Matsushita, Satoshi ; Kurihara, Hidetake ; Watanabe, Makino ; Okada, Takao ; Sakai, Tatsuo ; Amano, Atsushi
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Background: Connexin43 (Cx43), a gap
junction protein, mediates cell-cell communication via
electrical and chemical coupling. Ischemic stress of the
cardiac muscle interrupts intercellular communication by
changing the distribution and phosphorylation status of
Cx43. This may be a factor contributing to reentrant
arrhythmia. The calcium channel blocker diltiazem is
known for its protective and anti-arrhythmogenic effect
in ischemic heart disease. In this study, we assess the
effect of diltiazem pretreatment upon ischemia-induced
phosphorylation change of Cx43
Methods: Langendorff preparations of isolated
Wistar rat hearts were performed. After stabilization,
hearts were treated with (D+) or without diltiazem (D-),
then subjected to hypoxia-reoxygenation. After
perfusion, the left ventricle was prepared for
immunocytochemistry and immunoblot analysis.
Results: During perfusion, left ventricular function
was better in the D+ group than the D- group.
Immunostaining of the heart indicated that
dephosphorylated Cx43 (dpCx43) signal was increased
after hypoxic perfusion, and this finding was confirmed
by immunoblot data. The quantitative area analysis of
dpCx43 using the immunohistochemical approach
showed that the dpCx43-positive area was enlarged, as
the hypoxic perfusion time was longer, and it was
reduced by pretreatment of diltiazem. There was a
negative correlation between the dpCx43 area and
%RPP (rate-pressure product), calculated by heart rate
and contraction force.
Conclusions: Pretreatment of diltiazem could protect
the heart against hypoxia-reoxygenation injury by attenuation of dephosphorylation of Cx43. The antiarrhythmic
mechanism of diltiazem may include the
preservation of phosphorylation status of Cx43 after
hypoxia-reoxygenation injury.
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