Modification of myofibrillar responsiveness to Ca++ as an inotropic mechanism.

Intracellular Ca++ transients were monitored in preparations of mammalian heart muscle in which multiple superficial cells had been microinjected with the Ca++-sensitive bioluminescent protein aequorin. The relationship between changes in intracellular [Ca++] and changes in isometric tension development were studied under a variety of conditions in which experiments with "skinned" cardiac muscle preparations have indicated that alterations take place in the sensitivity of the myofilaments to Ca++. In each case (changes in muscle length, changes in intracellular pH, exposure to caffeine or theophylline, exposure to catecholamines, exposure to sulmazole), the relationship between the aequorin signal and the developed tension changed in ways that suggest that alterations in myofibrillar Ca++ sensitivity play an important role in the responses of intact myocardial cells to these inotropic interventions. Studies of the positive inotropic response of the rabbit papillary muscle to alpha-adrenoceptor stimulation indicate that an increase in myofibrillar responsiveness to Ca++ must play an important role in the genesis of this response as well.