Calcium Waves in Atrial Cells

Project: Research project

Description

DESCRIPTION (provided by applicant):
This training grant is designed to provide the principal investigator (Pl)
with the necessary didactic training and laboratory experience to become an
independent biomedical researcher. The PI?s immediate career goals are to
acquire the knowledge in using supercomputers and the experimental skills of
electrophysiology and microscopy necessary to develop a quantitative
understanding of atrial excitation-contraction (E-C) coupling. The Pl?s long-term
career goal is to lead a multidisciplinary team of physiologists,
mathematicians, physicians, and computer programmers in developing a
quantitative understanding of both normal and pathological E-C coupling in
atrial cells. Mammalian ventricular cells have an extensive transverse(t)-tubular
system that rapidly conducts the action potential from the cell
surface to the interior triggering a near synchronous calcium (Ca) release
from the sarcoplasmic reticulum (SR) and activation of myofibrils throughout
the cell. Atrial cells lack an extensive t-tubular system. How Ca
release from the SR far from the cell surface is triggered is unclear. The
overall hypothesis is that in atrial cells, Ca entry during an action
potential triggers regenerative Ca release from the SR at the cell surface and
this regenerative Ca release ("Ca wave") propagates as a wave radially to the
center of the cell. The Specific Aims are: (1) Test this hypothesis by
correlating atrial single-cell contraction rate and magnitude with the Ca
wave?s velocity and amplitude using video rate 2-dimensional confocal
microscopy and fluorescent Ca indicators. (2) Develop a mathematical model of
the atrial cell Ca control system and solve the model numerically using
supercomputers. (3) Evaluate the model by comparing the model?s predictions
with experimental measurements of Ca waves in voltage-clamped atrial cells
using confocal microscopy. A quantitative model of the atrial Ca control
system is necessary for understanding both normal E-C coupling and the origins
of pathological spontaneous Ca waves, which recent data suggest can trigger
atrial arrhythmias.
StatusFinished
Effective start/end date1/22/0211/30/06

Funding

  • National Institutes of Health: $26,948.00
  • National Institutes of Health: $148,343.00
  • National Institutes of Health: $100,000.00
  • National Institutes of Health: $126,948.00
  • National Institutes of Health: $126,948.00

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Calcium Signaling
Calcium
Excitation Contraction Coupling
Sarcoplasmic Reticulum
Research Personnel
Myofibrils
Organized Financing
Confocal Microscopy
Action Potentials
Cardiac Arrhythmias
Microscopy
Theoretical Models
Physicians

ASJC

  • Medicine(all)