Hypoxia, calcium fluxes, and inotropic state: studies in cultured heart cells

Methods have been developed for the study of cellular mechanisms underlying a variety of physiologic and pathophysiologic phenomena using cultured chick embryo heart cells. These spontaneously beating monolayer preparations lack appreciable diffusion barriers, and interstitial space components can be defined and controlled conveniently. These properties facilitate the measurement of transmembrane fluxes and cellular contents of sodium, potassium, and calcium. Concomitantly, methods have been developed to measure the contractile state as reflected in the amplitude and velocity of movement of individual myocytes in the culture. Experiments are described in which the contractile responses of cultured heart cells to graded hypoxia demonstrated a critical PO2 level around 12 mm Hg, below which progressive impairment of contractile function occurred. In preparations with iodoacetate-induced glycolytic blockade, enhanced sensitivity to hypoxia occurred. Although experiments are described, demonstrating the applicability of this model system to the study of problems including the mechanism of cardiac glycoside-induced increases in inotropic state and the definition of calcium flux pathways important in excitation-contraction coupling.