PROTEIN-KINASE-C ENHANCES MYOSIN LIGHT-CHAIN KINASE EFFECTS ON FORCE DEVELOPMENT AND ATPASE ACTIVITY IN RAT SINGLE SKINNED CARDIAC-CELLS

Many neurohormones alter the force of cardiac contraction by variations in the intracellular Ca2+ concentration. alpha-1-Adrenergic and muscarinic stimulations, rather, modify the sensitivity of contractile proteins to Ca2+ ions. Measuring the force developed by rat single skinned cardiac cells, the present study demonstrates that the Ca2+-calmodulin-myosin light-chain kinase (MLCK) complex induces a large increase in Ca2+ sensitivity (0.14 pCa unit) of these easily accessible myofilaments. This increase is further enhanced by up to 0.19 pCa unit when protein kinase C (PKC) is added together with MLCK. Similarly, the Ca2+ ATPase activity of skinned cells in suspension is increased in the presence of MLCK and further in the presence of both kinases. P-32-labelling and SDS/PAGE show that these changes are associated with light-chain 2 (LC2) phosphorylation together with phosphorylation of troponin I and troponin T when PKC is added. Although to a smaller extent than in smooth muscle, phosphorylation of cardiac myosin LC2 may be involved in the modulation of heart contractility.