TY - JOUR
T1 - Ageing is associated with a decrease in the number of sarcolemmal ATP-sensitive K+ channels in a gender-dependent manner.
AU - Ranki, HJ
AU - Crawford, Russell Mckenzie
AU - Budas, GR
AU - Jovanovic, A
PY - 2002/3/31
Y1 - 2002/3/31
N2 - The opening of sarcolemmal K-ATP channels is considered to be an important endogenous cardioprotective mechanism. On the other hand, age-dependent changes in the myocardial susceptibility to ischemia and hypoxia have been observed in different species, including humans. Here, we have hypothesized that aging might be associated with the changes in sarcolemmal K-ATP channels. Therefore, the main objective of the present study was to establish whether aging changes expression of cardiac sarcolemmal ATP-sensitive K+ (K-ATP) channels. RT-PCR using primers specific for K-ATP channel subunits, Kir6.2, Kir6.1 and SUR2A subunits was performed using total RNA from guinea-pig ventricular tissue. Whole cell electrophysiology was done on isolated guinea-pig ventricular cardiomyocytes. Western blotting using anti-Kir6.2 and anti-SUR2A antibodies was performed on cardiac membrane fraction. Tissue and cells were harvested from young and old, male and female guinea-pigs. RT-PCR analysis did not reveal significant age-related changes in levels of Kir6.1 or Kir6.2 mRNAs. However, levels of SUR2A were significantly lower in old than in young females. Such age-differences were not observed with cardiac tissue from male animals. In both old and young males, pinacidil (100 muM) induced outward currents. The difference between current density of pinacidil-sensitive component in females, but not males, was statistically significant. Western blotting analysis revealed higher levels of Kir6.2 and SUR2A proteins in cardiac membrane fraction from young than old females. The present study demonstrates that in females, but not males, aging is associated with decrease in number of cardiac K-ATP channels which is due to decrease in levels of the SUR2A subunit. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
AB - The opening of sarcolemmal K-ATP channels is considered to be an important endogenous cardioprotective mechanism. On the other hand, age-dependent changes in the myocardial susceptibility to ischemia and hypoxia have been observed in different species, including humans. Here, we have hypothesized that aging might be associated with the changes in sarcolemmal K-ATP channels. Therefore, the main objective of the present study was to establish whether aging changes expression of cardiac sarcolemmal ATP-sensitive K+ (K-ATP) channels. RT-PCR using primers specific for K-ATP channel subunits, Kir6.2, Kir6.1 and SUR2A subunits was performed using total RNA from guinea-pig ventricular tissue. Whole cell electrophysiology was done on isolated guinea-pig ventricular cardiomyocytes. Western blotting using anti-Kir6.2 and anti-SUR2A antibodies was performed on cardiac membrane fraction. Tissue and cells were harvested from young and old, male and female guinea-pigs. RT-PCR analysis did not reveal significant age-related changes in levels of Kir6.1 or Kir6.2 mRNAs. However, levels of SUR2A were significantly lower in old than in young females. Such age-differences were not observed with cardiac tissue from male animals. In both old and young males, pinacidil (100 muM) induced outward currents. The difference between current density of pinacidil-sensitive component in females, but not males, was statistically significant. Western blotting analysis revealed higher levels of Kir6.2 and SUR2A proteins in cardiac membrane fraction from young than old females. The present study demonstrates that in females, but not males, aging is associated with decrease in number of cardiac K-ATP channels which is due to decrease in levels of the SUR2A subunit. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
KW - aging
KW - gender
KW - K-ATP channels
KW - cardioprotection
KW - heart
KW - PREVENTS MEMBRANE DEPOLARIZATION
KW - CHEMICAL HYPOXIA-REOXYGENATION
KW - METABOLIC STRESS
KW - POTASSIUM CHANNELS
KW - RAT HEARTS
KW - DISEASE
KW - CONJUNCTION
KW - SUBUNITS
KW - DELIVERY
KW - THERAPY
UR - http://www.scopus.com/inward/record.url?scp=0037204531&partnerID=8YFLogxK
UR - http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T31-44R2SMP-2&_coverDate=03%2F31%2F2002&_alid=482995426&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4933&_sort=d&view=c&_acct=C000050565&_version=1&_urlVersion=0&_userid=1026342&md5=8c56547e1bf49b6896cc9bfd2f4f7f69
U2 - 10.1016/S0047-6374(01)00415-8
DO - 10.1016/S0047-6374(01)00415-8
M3 - Article
SN - 0047-6374
VL - 123
SP - 695
EP - 705
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 6
ER -