Developmental Differences and Regional Similarities in the Responses of Rat Cardiac Skinned Muscles to Acidosis, Inorganic Phosphate and Caffeine

The Ca2+sensitivity of cardiac myofibrillar force production can be decreased by acidosis or inorganic phosphate (Pi) and increased by caffeine. To investigate whether the source of tissue influences the potency of these agents, we compared the actions of acidosis (change of pH from 7.0 to 6.2), Piand caffeine (both 20 m ) on force production of skinned cardiac muscles from adult ventricle, adult atrium and neonate ventricle of the rat. Maximum Ca2+-activated force was reduced by all three interventions and the responses of the different muscle types to a given intervention were similar. Acidosis reduced myofibrillar Ca2+sensitivity by 1.09 and 1.04 pCa units in adult ventricle and atrium, respectively, and Pireduced it by 0.19 and 0.22 pCa units. However, each effect was only one-third as great in the neonate ventricle, which showed falls of 0.33 pCa units for acidosis and 0.06 for Pi. In contrast, caffeine raised the Ca2+sensitivity by the same amount ( 0.4 pCa units) in all three muscle types. The differential effect between adult and neonate seen with both acidosis and Pisuggests some similarity in the mechanisms by which these factors decrease Ca2+sensitivity. In contrast, the equal effects of caffeine on neonate and adult suggests that caffeine acts by a completely different mechanism. The lower pH- and Pi-sensitivity of the neonatal ventricle can help to explain why neonatal and adult myocardium exhibit differential force responses to ischaemia (or hypoxia alone).