Vol. 283, Issue 1, H440-H447, July 2002
Opening of mitochondrial KATP channel occurs
downstream of PKC-
activation in the mechanism of
preconditioning
Yoshito
Ohnuma,
Tetsuji
Miura,
Takayuki
Miki,
Masaya
Tanno,
Atsushi
Kuno,
Akihito
Tsuchida, and
Kazuaki
Shimamoto
Second Department of Internal Medicine, Sapporo Medical
University School of Medicine, Sapporo 060-8543, Japan
We examined
whether the mitochondrial ATP-sensitive K channel (KATP) is
an effector downstream of protein kinase C-
(PKC-) in the
mechanism of preconditioning (PC) in isolated rabbit hearts. PC with
two cycles of 5-min ischemia/5-min reperfusion before 30-min
global ischemia reduced infarction from 50.3 ± 6.8% of the left ventricle to 20.3 ± 3.7%. PC significantly increased PKC- protein in the particulate fraction from 51 ± 4% of the total to 60 ± 4%, whereas no translocation was observed for
PKC-
and PKC-
. In mitochondria separated from the other
particulate fractions, PC increased the PKC- level by 50%. Infusion
of 5-hydroxydecanoate (5-HD), a mitochondrial KATP blocker,
after PC abolished the cardioprotection of PC, whereas PKC-
translocation by PC was not interfered with 5-HD. Diazoxide, a
mitochondrial KATP opener, infused 10 min before ischemia limited infarct size to 5.2 ± 1.4%, but this
agent neither translocated PKC- by itself nor accelerated PKC-
translocation after ischemia. Together with the results of
earlier studies showing mitochondrial KATP opening by PKC,
the present results suggest that mitochondrial
KATP-mediated cardioprotection occurs subsequent to PKC-
activation by PC.
mitochondria; protein kinase C; infarct size
