AJP - Heart and Circulatory Physiology, Vol 257, Issue 6 1843-H1850, Copyright © 1989 by American Physiological Society
Modulation of effect of extracellular calcium buffering in cardiac muscle
S. Ginsburg and Y. Shimoni
Department of Physiology, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
The buffering of extracellular calcium by citrate, with identical free
calcium levels in the buffered and unbuffered medium, was previously found
to markedly reduce tension in frog and guinea pig atria. We now report the
following results. 1) In guinea pig, postest contractions are not reduced
by citrate. 2) In frog the negative inotropic effect of citrate is greatly
attenuated by partially replacing extracellular sodium concentration
([Na+]o) with lithium or sucrose. In contrast, in low [Na+]o, sodium salts
of weak acids (which cause intracellular acidosis) still reduce tension.
These findings strongly support the suggestion that citrate does not reduce
tension directly, e.g., by causing intracellular acidosis or by reducing
voltage-dependent calcium currents. 3) Higher stimulation rates also
decrease the effect of citrate. 4) Treatment with neuraminidase or
phospholipase D, both of which alter sarcolemmal calcium binding, dose not
change the effect of citrate. 5) The positive inotropic effect of
strophanthidin is reversibly lost in the presence of citrate. Our results
provide a different, novel approach to support earlier suggestions that the
extracellular matrix and/or the sarcolemma contain abundant calcium-binding
sites that supply some of the calcium for contraction. Citrate presumably
binds calcium more strongly, thereby "trapping" calcium released from the
extracellular "stores," so that less calcium is made available for
contraction. The inotropic effect of cardiac glycosides may also depend on
the calcium that is bound to these stores.
