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 d ecreased by acidosis or inorganic phosphate (P-i) and increased by caf feine, To investigate whether the source of tissue influences the pote ncy of these agents, we compared the actions of acidosis (change of pH from 7.0 to 6.2), P-i and caffeine (both 20 mM) on force production o f skinned cardiac muscles from adult ventricle, adult atrium and neona te ventricle of the rat. Maximum Ca2+-activated force was reduced by a ll three interventions and the responses of the different muscle types to a given intervention were similar, Acidosis reduced myofibrillar C a2+ sensitivity by 1.09 and 1.04 pCa units in adult ventricle and atri um, respectively, and P-i reduced it by 0.19 and 0.22 pCa units. Howev er, 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 P-i. In contrast, caffeine raised the Ca2+ sensitivity by the same amount (si milar to 0.4 pCa units) in all three muscle types. The differential ef fect between adult and neonate seen with both acidosis and P-i suggest s some similarity in the mechanisms by which these factors decrease Ca 2+ sensitivity. In contrast, the equal effects of caffeine on neonate and adult suggests that caffeine acts by a completely different mechan ism. The lower pH- and P-i-sensitivity of the neonatal ventricle can h elp to explain why neonatal and adult myocardium exhibit differential force responses to ischaemia (or hypoxia alone). (C) 1996 Academic Pre ss Limited