Abstract
To investigate the mechanisms regulating excitation-metabolic coupling
in rabbit epicardial, midmyocardial, and endocardial ventricular
myocytes we extended the LabHEART model (Puglisi JL and Bers DM.
Am J Physiol Cell Physiol 281: C2049-C2060, 2001). We incorporated
equations for Ca(2+) and Mg(2+) buffering by ATP and ADP, equations
for nucleotide regulation of ATP-sensitive K(+) channel and L-type
Ca(2+) channel, Na(+)-K(+)-ATPase, and sarcolemmal and sarcoplasmic
Ca(2+)-ATPases, and equations describing the basic pathways (creatine
and adenylate kinase reactions) known to communicate the flux changes
generated by intracellular ATPases. Under normal conditions and during
20 min of ischemia, the three regions were characterized by different
I(Na), I(to), I(Kr), I(Ks), and I(Kp) channel properties. The results
indicate that the ATP-sensitive K(+) channel is activated by the
smallest reduction in ATP in epicardial cells and largest in endocardial
cells when cytosolic ADP, AMP, PCr, Cr, P(i), total Mg(2+), Na(+),
K(+), Ca(2+), and pH diastolic levels are normal. The model predicts
that only K(ATP) ionophore (Kir6.2 subunit) and not the regulatory
subunit (SUR2A) might differ from endocardium to epicardium. The
analysis suggests that during ischemia, the inhomogeneous accumulation
of the metabolites in the tissue sublayers may alter in a very irregular
manner the K(ATP) channel opening through metabolic interactions
with the endogenous PI cascade (PIP(2), PIP) that in turn may cause
differential action potential shortening among the ventricular myocyte
subtypes. The model predictions are in qualitative agreement with
experimental data measured under normal and ischemic conditions in
rabbit ventricular myocytes.
- action
- adenosine
- animals;
- atp-binding
- atpase,
- atpases,
- calcium
- calcium,
- calcium-transporting
- cardiac,
- cardiovascular;
- cassette
- channel
- channels,
- computer
- concentration;
- creatine,
- diphosphate,
- drug,
- endocardium,
- enzymology/metabolism;
- gating;
- heart
- hydrogen-ion
- inwardly
- ion
- ischemia,
- l-type,
- magnesium,
- metabolism
- metabolism/physiopathology;
- metabolism;
- models,
- monophosphate,
- myocardial
- myocytes,
- pericardium,
- phosphocreatine,
- potassium
- potassium,
- potentials;
- rabbits;
- receptors,
- rectifying,
- reticulum
- sarcoplasmic
- signal
- simulation;
- sodium-potassium-exchanging
- transduction;
Users
Please
log in to take part in the discussion (add own reviews or comments).