View Clinical Trial (Medical Research Study)
Calcium Current in Human Atrial Myocytes
| City: |
|
Atlanta |
| State: |
|
Georgia |
| Zip Code: |
|
30322 |
| Conditions: |
|
Congenital Heart Disease - Tetralogy of Fallot |
| Purpose: |
|
We will use small pieces of human hearts which are removed as part of a required surgical
procedure to study how calcium ions pass through the membrane of heart cells in order to
tell the heart cell how much force to contract with when the heart beats. We will also
study the proteins and RNA of these pieces to determine how the newborn heart cells control
their force of contraction differently from adult heart cells. Our hypothesis is that
infant hearts have different regulation of calcium entry than adult hearts.
|
| Study Summary: |
|
Extrapolating pharmacological and surgical therapies from adult (AD) studies to infant (INF)
patients is problematic because the knowledge of cellular electrophysiology and molecular
biology of human INF heart cells is limited. We have studied developmental differences in
rabbit ventricular cells and now extend these studies to atrial and ventricular cells
isolated from AD, young adult (YAD) or INF patients. SA 1: Developmental differences in
transient outward current of atrial cells. We will extend our studies to isolated cells and
tissue from YADs (age 14-20). In addition, several other accessory beta-subunits have been
found in cardiac myocytes and may interact with Kv channels and regulate the function of
these channels. We will determine relative amounts of these putative regulators of human
atrial Ito to determine which correlate with developmental changes in Ito kinetics.SA2:
Developmental differences in amplitude and regulation of calcium current in atrial cells.
We hypothesize that INF atrial cells have tonic inhibition of adenylyl cyclase (and thus of
ICa) mediated by inhibitory G proteins, possibly related to constitutive activity of the
adenosine A1 receptor, and that, compared to AD or YAD cells, have greater sensitivity to
inhibitors of phosphatases and phosphodiesterases, and that developmental changes in basal
ICa amplitude and beta-sympathetic modulation correlate with inhibitory G protein levels,
receptor numbers for M2 and A1 receptors, and constitutive inhibitory activity. SA3:
Modulation of atrial cell calcium transients by changes in AP waveform and developmental
age. We will test the hypothesis that prolongation of the early repolarization phase of the
AP increases Ca2+ entry and that YAD cells have faster removal of Ca2+ from cytoplasm than
INF cells and we will determine if the Na- Ca2+ exchange current (INCX) is greater in INF
vs. AD or YAD cells. SA4: Developmental differences in Ca current and transients in
ventricular cells. We propose that INF cells and tissue have lower basal ICa, lower potency
for ISO stimulation, higher levels of Gialpha3 and A1 receptors, greater inhibitory potency
for adenosine, and tonic inhibition of ICa. We also propose that the YAD cells have lower
levels of NCX and lower INCX, higher levels of SERCA and faster removal of Ca2+ from the
cytoplasm. Previous animal studies have indicated various developmental changes in cardiac
cells. We will specifically study human postnatal developmental changes in Ito, regulation
of ICa and intracellular Ca2+ transients.
|
| Criteria: |
|
Inclusion Criteria:
patients undergoing cardiopulmonary bypass surgery
Exclusion Criteria:
|
| NCT ID: |
|
NCT00243776 |
| Primary Contact: |
|
Principal Investigator
Ronald W Joyner, M.D., Ph.D.
Emory University
Ronald w JOYNER, M.D./ Ph.D
Phone: 404 727 5747
Email: RJOYNER@CELLBIO.EMORY.EDU
|
| Backup Contact: |
|
Email: mwagner@cellbio.emory.edu
Mary b Wagner, Ph.D.
Phone: 404 727 5747
|
| Location Contact: |
|
Atlanta, Georgia 30322
United States
There is no listed contact information for this specific location.
Site Status: Recruiting |
| Data Source: |
|
ClinicalTrials.gov |
| Date Processed: |
|
May 22, 2013 |
| Modifications to this listing: |
|
Only selected fields are shown, please use the link
below to view all information about this clinical trial. |
|
Click to view Full Listing
|