AJP - Heart and Circulatory Physiology, Vol 248, Issue 1 75-H81, Copyright © 1985 by American Physiological Society
Inhibition of sarcolemmal Na+-K+-ATPase by palmitoyl carnitine: potentiation by propranolol
J. H. Kramer and W. B. Weglicki
Native sarcolemma (SL) from adult canine cardiac myocytes (Na+-K+-ATPase
activity 74.2 +/- 3.0 mumol X mg-1 X h-1) was preincubated (10 min, 37
degrees C, pH 7.2) with 1) 20-600 microM palmitoyl carnitine, 2) 250 nM-2.5
mM propranolol, or 3) 20-600 microM palmitoyl carnitine plus propranolol at
various concentrations (0.0, 0.025, 0.25, 0.5, 1.0, and 2.5 mM); after
preincubation, Na+-K+-ATPase activity was assayed. Palmitoyl carnitine
alone (series 1) had no effect on ATPase activity over the range of 20-400
microM but was inhibitory (30%) at 600 microM. Propranolol alone (series 2)
did not alter ATPase activity at any concentration. When SL membranes were
exposed to both palmitoyl carnitine and propranolol (series 3), a
dose-dependent inhibition of ATPase activity was observed. The inhibitory
effect was not reversed by 3.0% bovine serum albumin. Propranolol
concentrations greater than 0.025 mM significantly inhibited the activity
of SL exposed to palmitoyl carnitine (above 150 microM). Palmitoyl
carnitine and propranolol do not have to be added simultaneously to produce
combined inhibition. Activity was inhibited 50% when SL were pretreated
with 100 microM palmitoyl carnitine followed by addition of 2.5 mM
propranolol no inhibition occurred if preincubation conditions were
reversed. Thus exposure of SL to propranolol and reported physiological
levels of palmitoyl carnitine leads to irreversible inhibition of the
Na+-K+-ATPase, which may be due to the combined membrane-perturbant actions
of these amphipathic agents.
