SARCOLEMMAL CALCIUM TRANSPORT MECHANISMS IN HEART CELLS

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.Description
StatusFinished
Effective start/end date4/1/9011/30/01

Funding

  • National Institutes of Health: $272,480.00
  • National Institutes of Health: $106,164.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $133,639.00
  • National Institutes of Health: $113,449.00
  • National Institutes of Health: $266,770.00
  • National Institutes of Health
  • National Institutes of Health

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Adenosine Triphosphatases
Calcium
Homeostasis
Cardiac Myocytes
Excitation Contraction Coupling
Ions
Calcium-Transporting ATPases
Muscle Cells
Electrodes
Buffers
Cell Membrane
Sarcoplasmic Reticulum
Membranes
Action Potentials
Confocal Microscopy

ASJC

  • Medicine(all)