AJP - Heart and Circulatory Physiology, Vol 257, Issue 1 226-H237, Copyright © 1989 by American Physiological Society
Role of calcium in caffeine-norepinephrine interactions in cardiac Purkinje fibers
H. Satoh and M. Vassalle
Department of Physiology, State University of New York, Brooklyn 11203.
Caffeine-norepinephrine interactions were studied in canine cardiac
Purkinje fibers perfused in vitro. Caffeine (0.5-1 mM) or theophylline
(0.5-1 mM) increased and then decreased contractile force in the absence
and presence of 0.5-10 microM norepinephrine (NE) [in high extracellular
calcium concentration ([Ca]o) caffeine only decreases force]. Occasionally,
caffeine only decreased force in the presence of NE. In the presence of NE
and 12 mM (sometimes even 4 mM) extracellular potassium concentration,
caffeine did not decrease force below the precaffeine level. Reciprocally,
in 0.5-2 mM caffeine NE increased force, although less than in the absence
of caffeine. Even in 9 mM caffeine, NE increased force but slowed the final
phase three repolarization of the action potential. Both NE and 8.1 mM
[Ca]o increased force, but NE decreased force in the presence of high
[Ca]o. In NE and propranolol (or propranolol alone), caffeine only
increased force, whereas it had the usual effects in the presence of
methoxamine or phenotolamine. In the presence of iodoacetic acid and
2-deoxy-D-glucose, NE caused contracture and caffeine exaggerated it. In
contrast, in NE and 2 mM Mn, caffeine only increased force. It is concluded
that initially NE diminishes the cytoplasmic calcium overload induced by
caffeine (by promoting Ca uptake into the sarcoplasmic reticulum) and
subsequently enhances it (by increasing the slow inward current).
