INTRACELLULAR-DISTRIBUTION OF ADENYLATE-CYCLASE IN HUMAN CARDIOCYTES DETERMINED BY ELECTRON-MICROSCOPIC CYTOCHEMISTRY

Subcellular localization of adenylate cyclase (AC) in human cardiocyte s was studied by electron microscopic cytochemistry using ventricular biopsies from various diseased hearts. In addition to the weak enzyme activity on the sarcolemma, the intense reaction products of AC were d emonstrated within distinctive morphologic components of sarcoplasmic reticulum, nuclear envelope, and other internal membranes such as para llel lamellar structures and interlaced tubular structures in the peri nuclear regions and stacked membranous structures beneath sarcolemma i n cardiocytes. The distribution and intensity of cytochemical activity within different organelles was variable among biopsy cases. The reac tion products of AC cytochemistry within the sarcoplasmic reticulum co uld be related to signal transduction targeting Ca2+ handling by the o rganella. Cytochemical activity within the nuclear envelope and perinu clear internal membranes possibly reflects AC participation in a signa l function to regulate nuclear activity, such as gene expression. Cyto chemical distribution of the enzyme in membranous structures beneath t he sarcolemma is most likely related to hormone receptors and the link ed activity of AC. The subcellular distribution of AC on various inter nal membrane structures in cardiocytes may reflect compartmentalizatio n of the enzyme at individual intracellular sites to regulate a prefer ential specific signal function among multiple potential signal transd uctions by a cascade of AC, cyclic AMP, and cyclic AMP-dependent prote in kinase. Alternatively, subcellular localization of the reaction pro ducts may reflect local enzyme synthesis or represent sites of enzyme transport, e.g., to terminal localization beneath the sarcolemma. (C) 1998 Wiley-Liss, Inc.