Project Details
Description
The goal of this proposal is to study the importance of sarcolemmal calcium
transport mechanisms, the Na/Ca exchange mechanism and the Ca-ATPase, in
regulating the intracellular Ca2+ homeostasis of the cardiac cell. The
proposed experiments will examine 1) under what conditions the Na/Ca
exchange mechanism controls "resting" or steady state [Ca2+], 2) how Na/Ca
exchange regulates the size of the stimulate [Ca2=}, transient and 3) the
role of the Ca-ATPase in controlling [Ca2+], homeostasis in cardiac cells,
experiments will focus on a detailed kinetic analysis of the Ca2+ flux via
Na/Ca exchange and the Ca2+ extrusion by the Ca-ATPase. To accomplish
these objectives, experiments will be performed on single cardiac
ventricular myocytes which are voltage clamped with a low resistance patch
pipette. The patch electrode will contain fluorescent indicator for
measurement of Ca2+, Na+ or H+ as well as specific concentrations of
various ions (Na+, for example) and Ca2+ buffers so that ionic gradients
across the cell membrane and cellular Ca2+ buffering can be controlled.
This experimental technique will allow for simultaneous measurement of
membrane currents, intracellular ion concentration and membrane Ca2+
transport. In this way, the amount of Ca2+ flux via the Na/Ca exchange
mechanism and the Ca2+-ATPase can be accurately determined under a variety
of conditions.
Because the Na/Ca exchanger and the Ca-ATPase are responsible for
maintaining Ca2+ homeostasis within the cardiac cell, they play a critical
role in controlling cell contraction and the underlying Ca2+ Transient.
These sarcolemmal transport mechanisms may be particularly important under
pathological conditions when changes in [Ca2+], in response to increases in
intracellular Na+ and H+ concentrations may determine whether electrical
and mechanical disturbances will occur.
Status | Finished |
---|---|
Effective start/end date | 4/1/90 → 6/30/95 |
Funding
- National Heart, Lung, and Blood Institute
ASJC
- Cardiology and Cardiovascular Medicine
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