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First published online July 6, 2005
Journal of Experimental Biology 208, 2765-2772 (2005)
Published by The Company of Biologists 2005
doi: 10.1242/jeb.01704

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Cardioprotective effects of K_ATP channel activation during hypoxia in goldfish Carassius auratus

Jerri Chen, Julia X. Zhu, Ingred Wilson and John S. Cameron^*

Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA

View larger version (173K): [in a new window]   Fig. 1. Isolated ventricular myocytes from goldfish heart after exposure to 60 min hypoxia in a solution containing Trypan Blue. Most cells retained the elongated shape of those maintained under normoxic conditions, but some were unable to exclude the dye (left), indicating cellular damage. Scale bar, 50 µm.

View larger version (12K): [in a new window]   Fig. 2. Effects of moderate, substrate-free hypoxia on ventricular action potential duration (APD) in the isolated goldfish heart. APD in hypoxia was significantly shortened at 90% of full repolarization, but not at 50% (N=5). Inset shows representative action potential configuration in one experiment (normoxia at left). Values are means ± 1 S.E.M. **Significantly different from values recorded under normoxic conditions (P<0.01).

View larger version (11K): [in a new window]   Fig. 3. Effects of glibenclamide (5 µmol l–1), a KATP channel blocker, and L-NAME (50 µmol l–1), an inhibitor of nitric oxide synthase (NOS), on the percentage change in action potential duration at 90% repolarization (APD90) induced by hypoxia in goldfish ventricle (N=4). Hypoxia-induced APD90 shortening was eliminated by simultaneous exposure to either glibenclamide or L-NAME. Values are mean change ± 1 S.E.M.

View larger version (12K): [in a new window]   Fig. 4. Effects of presumed KATP activators on the percentage change in ventricular action potential duration (APD) under normoxic conditions. APD90 was shortened by 10, 30 and 60 min exposure to SNAP (100 µmol l–1), a nitric oxide (NO) donor (N=4), and by 10 min exposure to 8-Br-cGMP (200 µmol l–1), a stable cGMP analog (N=6). Diazoxide (50 µmol l–1), a specific mitochondrial KATP (mitoKATP) channel opener, did not significantly affect APD (N=6). Values shown are mean changes ± 1 S.E.M.

View larger version (8K): [in a new window]   Fig. 5. Effect of 60 min hypoxia in vitro on the incidence of cell staining by Trypan Blue. Under hypoxic conditions, a significantly greater percentage of cells was unable to exclude the stain compared to that observed in normoxia, suggesting cellular injury. A total of more than more than 500 myocytes were individually evaluated during six experiments; values are mean changes ± 1 S.E.M. ***Significantly different from values recorded in normoxia (P<0.001).

View larger version (20K): [in a new window]   Fig. 6. Cardioprotective effect of SNAP (100 µmol l–1) on the hypoxia-induced damage incurred by isolated myocytes in vitro. Figs 6 and 7 show the percent change in the total fraction of stained cells after 60 min hypoxia in the presence of various agents, compared to that recorded after hypoxia alone. Under hypoxic conditions, SNAP reduced the percentage of stained cells. In contrast, L-NAME, which blocks hypoxia-induced synthesis of NO, increased the percentage of stained cells when given alone, and eliminated the cardioprotective influence of SNAP when the two drugs were administered simultaneously.

View larger version (27K): [in a new window]   Fig. 7. Cardioprotective influence of the mitoKATP opener diazoxide (50 µmol l–1) and the stable cGMP analog 8-Br-cGMP (200 µmol l–1) on the hypoxia-induced damage incurred by isolated cells. This figure illustrates the percentage change in the total fraction of stained cells after 60 min hypoxia in the presence of various agents, compared to that recorded after hypoxia alone. Under hypoxic conditions, both diazoxide and 8-Br-cGMP decreased the percentage of stained cells vs that seen with hypoxia alone. Blockade of mitoKATP channel activity with 5-HD (100 µmol l–1) reduced but did not eliminate the beneficial effect of diazoxide, and did not affect the response to 8-Br-cGMP.