ca2 ph and the regulation of cardiac myofilament force and atpase activity when the ph surrounding myofilaments of striated muscle is reduced there is an inhibition of both the actinmyosin reaction as well as the ca2sensitivity of the myofilaments although the mechanism for the effect of acidic ph on ca2sensitivity has been controversial we have evidence for the hypothesis that acidic ph reduces the affinity of troponin c tnc for ca2 this effect of acidic ph depends not only on a direct effect of protons on ca2binding to tnc but also upon neighboring thin filament proteins especially tni the inhibitory component of the tn complex using fluorescent probes that report ca2binding to the regulatory sites of skeletal and cardiac tnc we have shown for example that acidic ph directly decreases the ca2affinity of tnc but only by a relatively small amount however with tnc in whole tn or in the tnitnc complex there is about a 2fold enhancement of the effects of acidic ph on ca2binding to tnc acidic ph decreases the affinity of skeletal tni for skeletal tnc and also influences the microenvironment of a probe positioned at cys133 of tni a region of interaction with tnc other evidence that the effects of acidic ph on ca2tnc activation of myofilaments are influenced by tni comes from studies with developing hearts in contrast to the case with the adult preparations ca2activation of detergent extracted fibers prepared from dog or rat hearts in the perinatal period are weakly affected by a drop in ph from 70 to 65 this difference in the effect of acidic ph appears to be due to a difference in the isoform population of tni and not to differences in isotype population or amount of tnc