Changes in membrane proteins in chronic mechanical overload of the heart.

Several data suggest that in species such as humans, dogs or guinea pigs, sarcomere protein changes do not explain the physiologic modifications that occur in the heart in response to chronic overload. In the guinea pig, e.g., the shortening velocity of an intact papillary muscle negatively correlates with the degree of hypertrophy while the shortening velocity of a skinned hypertrophied fiber does not correlate with heart weight. This review is an attempt to summarize quantitatively data concerning membrane proteins in chronic experimental cardiac overload. With that respect, 2 groups of proteins can be distinguished: (1) the group formed by the calcium-activated adenosine triphosphatase (Ca2(+)-ATPase) of the sarcoplasmic reticulum, the beta 1-adrenergic and muscarinic receptors and the low affinity isoform of the Na+K(+)-ATPase. The synthesis of these proteins is not activated by the process of hypertrophy and consequently their density diminished and their total number per myocyte or per ventricle is unchanged. (2) The second group is formed by the calcium channels and the high affinity isoform of the Na+K(+)-ATPase whose density, in contrast, is unchanged or even increases. Their synthesis is therefore stimulated commensurately with the degree of overload and their total number per myocyte is enhanced. These data suggest that search in the field of inotropes must take into account the fact that the keys that these drugs represent must be modeled as a function of the lock they have to fit into.