Project: Research project

Project Details


The general goal of this project is to understand the factors which control
the force of cardiac muscle contraction. More specifically the goals are
to elucidate mechanisms of excitation-contraction (E-C) coupling and to
gain insight into the interrelationships involved in the regulation of
intracellular Ca, Na, pH and K. The relative roles of Ca influx and SR Ca
release in the beat to beat control of cardiac contractility is an
important and controversial question. The planned studies will provide
direct information bearing on this issue. Experiments will be done using
double barreled Ca selective microelectrodes to measure transient
depletions of Cao which occur during individual beats reflecting phasic Ca
influx and cumulative depletions of Cao which occur over several beats
reflecting changes in Ca content. Studies of the regulation, interaction
and compartmentalization of intracellular Ca, Na and H ions will also be
undertaken using ion selective microelectrodes to continuously and directly
monitor the intracellular activities of these ions (in normal,
physiologically altered and ischemic conditions). Aspects of how these cations interact at sarcolemmal sites will be studied
in isolated cardiac sarcolemmal vesicles. These will allow assessment of
sidedness, symmetry, Na-Ca exchange, the Na-H exchange and Ca binding in
the sarcolemmal vesicles and the role these properties may have in the
control of cardiac contractility. Biophysical models will be developed to
describe how Ca, Na and H interact with sarcolemma bearing fixed negative
charges and to describe the effects of electrodiffusive forces acting on Ca
as it converges on a Ca channel. There is also much insight to be gained
in technically simple experiments taking advantage of pharmacological
agents, physiological manipulations and cardiac tissues with apparently
differing E-C coupling mechanisms. The results of the studies planned
should increase our understanding of the regulation of basic cardiac muscle
function in normal as well as pharmacologically and pathologically altered
Effective start/end date7/1/856/30/90


  • National Institutes of Health


  • Medicine(all)


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