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The First Evidence of Decreased Voltage‐Gated Ca 2+ Influx into Coronary Smooth Muscle in Ischemic Versus Non‐Ischemic Cardiomyopathy in Human Transplant Cardiectomy Samples
Author(s) -
Badin Jill K.,
Alloosh Mouhamad,
Chen Robert J.,
Hashmi Zubair A.,
Sturek Michael
Publication year - 2017
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.31.1_supplement.1017.17
Subject(s) - serca , ryanodine receptor , endoplasmic reticulum , depolarization , intracellular , medicine , chemistry , ischemic cardiomyopathy , cardiomyopathy , cardiology , biophysics , endocrinology , atpase , heart failure , ejection fraction , biology , biochemistry , enzyme
Ca 2+ regulation is pivotal to coronary smooth muscle (CSM) cells. Most Ca 2+ influx is routed via voltage‐gated Ca 2+ channels (VGCC). A fraction of the intracellular Ca 2+ is sequestered in the sarcoplasmic reticulum (SR) by the sarco‐endoplasmic reticulum Ca 2+ ATPase (SERCA) for later release via ryanodine receptors (RyR). Evidence in animal models of atherosclerosis clearly shows that intracellular Ca 2+ handling is dysregulated in metabolic syndrome. We tested the hypothesis that intracellular Ca 2+ handling would be dysregulated more in CSM in human ischemic (atherosclerotic) vs. non‐ischemic cardiomyopathy. Freshly isolated CSM cells from human hearts excised in transplant cardiectomy were loaded with the fluorescent intracellular Ca 2+ indicator fura‐2 and placed in a constant‐flow superfusion chamber. Membrane depolarization with 80 mM K + induced Ca 2+ influx largely via VGCCs and caused loading of the SR store. Caffeine‐induced SR Ca 2+ store release and undershoot after store depletion (SERCA activity) were also measured. Pure VGCC activity was calculated as the slope of Ba 2+ influx during superfusion with a 2 mM Ba 2+ solution, as Ba 2+ permeates VGCC but is not buffered by SERCA or Na‐Ca exchange. CSM isolated from hearts from patients with ischemic cardiomyopathy exhibited lower depolarization‐induced Ca 2+ influx, similar SR store release, similar undershoot, and trended towards lower barium slope than CSM from non‐ischemic patients. Overall, Ca 2+ influx via VGCC, but not Ca 2+ release or SERCA, may be more dysfunctional in ischemic than non‐ischemic cardiomyopathy. This is the first evidence of dysfunctional Ca 2+ influx in human atherosclerotic CSM.