This study describes the changes produced in the subcellular morphology of mammalian myocardium when perfusate sodium, calcium, and chloride concentrations are varied. By means of a recently developed perfusion technique, functioning dog papillary muscles were perfused with isotonic solutions of varying ionic compositions. Examination of the tissue in the electron microscope revealed that control muscles showed satisfactory preservation of ultrastructure, demonstrating that the protocol itself did not create significant morphological artefact. Low sodium chloride perfusion produced dilatation of both transverse tubules and longitudinal sarcoplasmic reticulum elements. Low sodium or high calcium concentrations produced dilation of tubular elements of the longitudinal sarcoplasmic reticulum while leaving transverse tubules intact. High calcium perfusion produced mitochondrial swelling and vacuolization. Mitochondrial precipitate, both crystalline and amorphous in form, was observed and presumed to be calcium phosphate, either alone or mixed with calcium carbonate. The possibility that the morphological changes observed might indicate subcellular loci of specific ion permeability is discussed. A correlation of the known kinetic behavior of sodium and calcium ions in mammalian myocardium with the ultrastructural alterations produced is suggested.

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