Changes in T-Tubules and Sarcoplasmic Reticulum in Ventricular Myocytes in Early Cardiac Hypertrophy in a Pressure Overload Rat Model.
OBJECTIVE
Pressure-overload (PO) causes cardiac hypertrophy (CH), and eventually leads to heart failure (HF). HF ventricular myocytes present transverse-tubules (TT) loss or disarrangement and decreased sarcoplasmic reticulum (SR) density, and both contribute to altered Ca2+ signaling and heart dysfunction. It has been shown that TT remodeling precedes HF, however, it is unknown whether SR structural and functional remodeling also starts early in CH.


METHODS
Using confocal microscopy, we assessed TT (with Di-8-ANNEPS) and SR (with SR-trapped Mag-Fluo-4) densities, as well as SR fluorophore diffusion (fluorescence recovery after photobleach; FRAP), cytosolic Ca2+ signaling and ex vivo cardiac performance in a PO rat hypertrophy model induced by abdominal aortic constriction (at 6 weeks).


RESULTS
Rats developed CH, while cardiac performance, basal and upon β-adrenergic stimulation, remained unaltered. TT density decreased by ∼14%, without spatial disarrangement, while SR density decreased by ∼7%. More important, FRAP was ∼30% slower, but with similar maximum recovery, suggesting decreased SR interconnectivity. Systolic and diastolic Ca2+ signaling and SR Ca2+ content were unaltered.


CONCLUSIONS
SR remodeling is an early CH event, similar to TT remodeling, appearing during compensated hypertrophy. Nevertheless, myocytes can withstand those moderate structural changes in SR and TT, preserving normal Ca2+ signaling and contractility.
Perla
P
Pérez-Treviño
Jorge
J
Pérez-Treviño
Cuauhtémoc
C
Borja-Villa
Noemí
N
García
Julio
J
Altamirano
D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D036681:Fluorescence Recovery After Photobleaching; D005456:Fluorescent Dyes / Q000737:chemistry; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D014966:Xanthenes / Q000737:chemistry
D000814:Aniline Compounds; C409648:Fluo 4; D005456:Fluorescent Dyes; D007477:Ions; D014966:Xanthenes; D002118:Calcium