Am. J. Respir. Crit. Care Med., Vol 149, No. 4, Apr 1994, 910-914.
Role of adenosine in the depolarization of hypoxic hamster diaphragm membrane in vitro
SA Esau
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
The resting membrane potential of in vitro hamster diaphragm muscle fibers
is depolarized on exposure to hypoxia. It was hypothesized that this
depolarization was mediated by adenosine. It was predicted that the
treatment of well-oxygenated hamster diaphragm muscle strips in vitro with
adenosine or adenosine agonists would depolarize the diaphragm fiber
membrane. Furthermore, resting membrane potential of hypoxic diaphragm
fibers would be repolarized by (1) the removal of adenosine by the enzyme
adenosine deaminase (ADA), or (2) the addition of an adenosine antagonist,
BW A1433. Adenosine (10(-4) M) depolarized the membrane by 8 +/- 1 mV (p
< 0.001). The adenosine agonist cyclopentyladenosine, which has
predominantly A1 receptor affinity, depolarized the membrane from -75.4 +/-
5.6 mV to -68.9 +/- 5.7 mV (p < 0.001). The A2 adenosine receptor
agonist 5'-N-ethylcarboxamide adenosine did not cause a significant
depolarization. The addition of ADA (2 unit/ml) to hypoxic muscle returned
the resting membrane potential to that of well-oxygenated fibers, p <
0.001 versus hypoxia. BW A1433 (3 x 10(-7)) also restored the membrane
potential of hypoxic muscle fibers from -72 +/- 1 mV to -79 +/- 1 mV (p
< 0.001). These observations suggest that adenosine via the A1 adenosine
receptor mediates the hypoxic depolarization of in vitro hamster diaphragm
muscle. A direct effect of adenosine on muscle membrane has not been
described previously.
