Meeting Abstract
P2.173 Monday, Jan. 5 Acclimation to Hypoxia Alters Gene Expression and KATP Channel Response to Acute Low Oxygen in the Hearts of Goldfish PARK, Sarah D.; ATHALE, Janhavi; NGUYEN, Thutrang T.; KANG, Esther; CHEN, J.; CAMERON, J.S.**; Wellesley College, MA jcameron@wellesley.edu
Goldfish (Carassius auratus) are extremely tolerant of environmental hypoxia and may retain normal cardiac function for several days in the complete absence of oxygen. Previous results suggest that the hypoxia-induced activation of cardiac ATP-sensitive potassium (KATP) channels, whether in sarcolemmal or mitochondrial membranes, serves to increase tolerance of low oxygen. We have characterized a nitric oxide (NO)- and cGMP-dependent signaling pathway by which this KATP channel activation occurs in acute hypoxia. The purpose of the present study was to resolve alterations in cardiac cell viability, KATP channel activity and gene expression in response to hypoxia acclimation. Goldfish were exposed to moderately hypoxic conditions (2.6 mg O2/l) for seven days at 22oC. Isolated cardiac myocytes from animals acclimated to hypoxia were significantly more tolerant of subsequent exposure to acute hypoxia in vitro than were cells from non-acclimated fish. The viability of cells from both groups was decreased by the NO-synthase (NOS) inhibitor L-NAME and enhanced by analogs of cGMP, although to different degrees. Quantitative real-time RT-PCR data indicated that KCNJ11, a gene coding for the pore-forming subunit of sarcolemmal KATP channels, was downregulated in response to hypoxia acclimation, while the expression of HIF1α (hypoxia inducible factor) was unchanged. These data indicate that prior whole-animal acclimation to chronic environmental hypoxia enhances cellular tolerance of subsequent low oxygen in this species, and suggest a role for the altered regulation of cardiac KATP channels in this response. (Supported by the Brachman Hoffman Fund and by an HHMI grant to Wellesley College)
