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Differences in I to and myofilament protein expression may underlie transmurally‐varying electromechanics in the canine left ventricle
Author(s) -
Campbell Stuart G.,
Flaim Sarah N.,
Leem Chae Hun,
McCulloch Andrew D.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.751.3
Subject(s) - ventricle , crossbridge , myofilament , medicine , myocyte , cardiology , chemistry , cats , biophysics , anatomy , endocrinology , biology , muscle contraction
Myocytes isolated from the endocardial, midmyocardial, and epicardial regions of the canine left ventricle (LV) possess distinct action potential morphologies, Ca 2+ transients (CaTs), and timecourses of unloaded shortening. Some of these differences have been linked to variable expression of Ca 2+ ‐handling and ion channel proteins. We used a computational model of myocyte electromechanics to test the hypothesis that identified variations in protein expression account for observed differences in mechanical function between epicardial (EPI), midmyocardial (MID), and endocardial (ENDO) cells. The ENDO cell model displayed a greater delay to onset of shortening compared with EPI and MID cells, in agreement with experiments. Time to onset of cell shortening was strongly affected by the magnitude of the transient outward K + current (I to ). Simulated shortening in response to experimentally measured ENDO and MID CaTs agreed well with experiments, while responses to the EPI CaT did not. Agreement between measured and simulated EPI shortening was improved by increasing the rate of crossbridge cycling. These results suggest important roles for I to and altered crossbridge kinetics in modulating electromechanical function within the canine LV. Supported by NSF grant BES‐0506252 and NIH grant P41 RR‐08605.