In the present study, on the basis of the diameter recorded in open caveolae, a significant proportion of caveolae recorded in the closed state in control cells should represent true closed vesicles. This is in accord with our observation that these closed caveolae are more distant from the sarcolemma than their open counterparts. We propose that the effect of Columbianadin swelling on reducing closed caveolae without affecting the open configuration underlies a cycle whereby stretch causes flattening of open caveolae in tandem with sarcolemmal incorporation of closed caveolae. Kohl and co-workers have previously reported evidence of stretchincorporation of closed caveolae in the adult myocardium. The idea of increased membrane tension acting as a feedback mechanism for vesicle recruitment is well established. Despite effects of swelling on the morphology of caveolae, we saw no translocation of Cav 1 or 3 from the caveolar fraction of the myocytes. Whilst some have reported stretch induced translocation of Cav 1, this is not a universal mechanism. For example, although the small G proteins Rac and RhoA translocate from caveolae in axially stretch neonatal cardiac myocytes, Cav 3 was shown to remain in caveolae. In the ventricular myocyte, the maximum volume and surface area increase recorded prior to lysis are much less than that reported for epithelial cells or fibroblasts, suggesting that the ventricular myocyte has less membrane reserves than these cell types. Groulx et al. recently addressed the source of membrane reserves during modest and Clinodiside-A extreme swelling in cultured cell lines by measuring surface area and volume changes with or without functional exocytotic pathways. Their data suggest that, in epithelial cells and fibrobasts, the majority of membrane reserves required during modest swelling come from excess surface membrane rather than intracellular membrane stores. The resulting loss of chondrocytes in the growth plate translates into decreased long bone growth and the disproportionate short stature found in PSACH. Intracellular retention and death of chondrocytes causes the loss of these proteins in the ECM.