A pH-sensitive interaction of troponin I with troponin C coupled with strongly binding cross-bridges in cardiac myofilament activation

Slow skeletal muscle troponin I (ssTnI) expressed predominantly in perinata l heart confers a marked resistance to acidic pH on Ca2+ regulation of card iac muscle contraction. To explore the molecular mechanism underlying this phenomenon, we investigated the roles of TnI isoforms (ssTnI and cardiac Tn I (cTnI)) in the thin filament activation by strongly binding cross-bridges , by exchanging troponin subunits in cardiac permeabilized muscle fibers. F etal cardiac muscle showed a marked resistance to acidic pH in activation o f the thin filament by strongly binding cross-bridges compared to adult mus cle, Exchanging ssTnI into adult fibers altered the pH sensitivity from adu lt to fetal type, indicating that ssTnI also confers a marked resistance to acidic pH on the crossbridge-induced thin filament activation. However, th e adult fibers containing ssTnI or cTnI but lacking TnC showed no pH sensit ivity. These findings provide the first evidence for the coupling between s trongly binding cross-bridges and a pH-sensitive interaction of TnI with Tn C in cardiac muscle contraction, as a molecular basis of the mechanism conf erring the differential pH sensitivity on Ca2+ regulation. (C) 2001 Academi c Press.